The Role of miR-23b in Cancer and Autoimmune Disease

Yu-Xin Guo; Na Wang; Wen-Cheng Wu; Cui-Qin Li; Rui-Heng Chen; Yuan Zhang; Xing Li

doi:10.1155/2021/6473038

The Role of miR-23b in Cancer and Autoimmune Disease

Guo, Yu-Xin;Wang, Na;Wu, Wen-Cheng;Li, Cui-Qin;Chen, Rui-Heng;Zhang, Yuan;Li, Xing 2021-11-03 00:00:00 Hindawi Journal of Oncology Volume 2021, Article ID 6473038, 9 pages https://doi.org/10.1155/2021/6473038 Review Article 1 2 1 1 3 Yu-Xin Guo , Na Wang , Wen-Cheng Wu , Cui-Qin Li , Rui-Heng Chen , 1 1 Yuan Zhang , and Xing Li National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest China, Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry (Shaanxi Normal University), 'e Ministry of Education, College of Life Sciences, Shaanxi Normal University, Xi’an, Shaanxi 710119, China Surgical Oncology Department, 'e First People’s Hospital of Tianshui, Tianshui, Gansu 741000, China 'e High School Aﬃliated to Shaanxi Normal University, Xi’an, Shaanxi 710119, China Correspondence should be addressed to Yuan Zhang; yuanzhang_bio@126.com and Xing Li; xingli_xian@126.com Received 27 May 2021; Accepted 18 October 2021; Published 3 November 2021 Academic Editor: Alessandro Granito Copyright © 2021 Yu-Xin Guo et al. .is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Short-stranded miRNAs are single-stranded RNA molecules involved in the regulation of gene expression. miRNAs are involved in a variety of cellular physiological processes, including cell proliferation, diﬀerentiation, and apoptosis. miR-23b have been identiﬁed to act both as oncogenes and as tumor suppressors. In addition, miR-23b is related to inﬂammation resistance to various autoimmune diseases and restrained inﬂammatory cell migration. .e characterization of the speciﬁc alterations in the patterns of miR-23b expression in cancer and autoimmune disease has great potential for identifying biomarkers for early disease diagnosis, as well as for potential therapeutic intervention in various diseases. In this review, we summarize the ever-expanding role of miR- 23b and its target genes in diﬀerent models and oﬀer insight into how this multifunctional miRNA modulates tumor cell proliferation and apoptosis or inﬂammatory cell activation, diﬀerentiation, and migration. divided into drug therapy and surgical treatment [7]. Drug 1. Introduction therapy refers to using drugs to destroy cancer cells, which is According to GLOBOCAN 2020, an assessment of cancer often used in clinical treatment. However, while killing morbidity and mortality, it is reported that the number of tumor cells, it will kill normal cells, so it often brings a series new cancer cases reached 19.3 million worldwide, and al- of side eﬀects, and chemotherapy does not have speciﬁcity most 10 million people died from cancer [1]. Moreover, for tumor tissue [8]. .us, most drug therapy has side eﬀects. breast cancer in women has overtaken lung cancer as the In addition, surgical treatment has adverse eﬀects such as primary cause of cancer incidence worldwide in 2020 [1, 2]. postoperative recurrence and slow healing. Importantly, .en, lung cancer is the second most frequently occurring their pathogenesis is also unclear [9]. .ese factors lead to cancer and the leading cause of cancer death [1]. Moreover, limited treatment options. .erefore, clarifying the speciﬁc changes in incidence and trends are closely related to the mechanism of the disease is of great signiﬁcance for the prevalence of tobacco [3, 4]. So, men are more likely to suﬀer treatment of the disease. from this disease. Among male cancers, liver cancer is also a Autoimmune disease refers to a disease in which the high incidence disease, ranking second in male mortality, body’s immune response to its antigen causes damage to its and the incidence of primary liver cancer has continued to own tissues [10]. Multiple sclerosis (MS) is an autoimmune rise since 2020 [4, 5]. Gastric cancer is a signiﬁcant disease demyelinating central nervous system (CNS) disease, in worldwide. Notably, in the United States, Canada, and the which immune cells inﬁltrate into the central nervous United Kingdom, the incidence of gastric cancer has in- system from the periphery, activate microglia and astrocytes, creased in both low- and high-risk young adults (younger and inhibit the diﬀerentiation of oligodendrocytes into ol- than 50 years) [6]. At present, the treatment of tumors can be igodendrocytes, resulting in pathological features such as 2 Journal of Oncology demyelination of myelin and axon [11, 12]. However, its MicroRNA regulation commonly occurs based on exact molecular mechanisms remain unclear. Besides, microRNA binding to the 3′ untranslated region (3′-UTR) of target mRNA [34]. MicroRNAs inhibit the expression of rheumatoid arthritis (RA), also a chronic autoimmune disease, aﬀects nearly 0.5%–1% of the population in the target genes by 3′-UTR combining with target RNAs [35]. world [13]. .e most common clinicopathological features .erefore, diﬀerent miRNA biological processes occur at of RA patients are cartilage degeneration and bone erosion diﬀerent sites in the cell, including RNA transcription, of large and small joints, leading to mobility diﬃculties and processing, transport, and RISC binding. Importantly, even disability in severe cases [14, 15]. Although there is miRNAs are critical for cell proliferation, diﬀerentiation, some genetic and environmental correlation, the speciﬁc and apoptosis [36]. miRNAs have been involved in many pathogenesis is not clear [16]. Systemic lupus eryth- cancers and neurodegenerative diseases, such as multiple ematosus (SLE) is also a chronic multisystem autoimmune sclerosis, Parkinson’s disease, and Alzheimer’s disease disorder. Although the cause of SLE is unknown, both [37, 38]. Overall, miRNAs play an essential part in the genetic and environmental elements are relevant to the occurrence and development of diseases [39]. disease mechanism [17]. Infection and environmental el- ements have been hypothesized to cause cell damage, 3. miR-23b Research Progress promote the exposure of autoantigens to the immune system, and cause B- and T-cell activation [18]. Indeed, .e miR-23b is due to the chromosomal region 9q22,32 clarifying the pathogenesis plays a critical role in the di- encoding mi-23b/27b/24-1 [23]. .e biogenetic process of agnosis and timely treatment of diseases. miR-23b is similar when miRNA is cut into miRNA double Small endogenous regulatory RNAs, also known as strand by Dicer enzyme-containing protein complex. One short-strand ribonucleic acid microRNAs (miRNAs), are strand is a passenger strand that will be degraded, and the critical posttranscriptional regulators of gene expression and other is miR-23b. miR-23b is involved in regulating normal were ﬁrst identiﬁed in C. elegans [19–21]. .ere are many physiological function, cell diﬀerentiation, and cellular kinds of miRNAs, among which miRNA-23b belongs to immunity [40]. .us, when the miR-23b homeostasis is miR-23b/27b/24-1 cluster [22]. miR-23b possessed regula- damaged, the normal physiological function of the cell will tory roles, especially in the development of cancer and also be aﬀected, and then diseases will occur. miR-23b can autonomic immune diseases [23]. In conclusion, this review induce a complex network of responses by directly targeting reveals miR-23b in various diseases, including cancer and multiple transcripts. To be speciﬁc, the changes of miR-23b autoimmune diseases, and its role in disease progression. expression were closely related to various transcription factors, such as TAB2, TAB3, NF-κB, tumor suppressor P53, estrogen receptor ER-α, mitogen-activated protein kinase 2. miRNA MAPK, activation protein AP-1, reactive oxygen species MicroRNA (miRNAs), which belonged to a category of ROS, and CCL7 [19, 41, 42]. It has been reported that miR- single-stranded RNA molecular, is not involved in coding 23b is closely related to the occurrence and development of a with a role in regulating gene expression [24, 25]. .e variety of diseases, including tumors and autoimmune formation of miRNA includes the multistage process. Firstly, diseases [23]. .is review summarized tumor-related dis- in the nucleus, RNA polymerase II or III transcripts miRNA- eases such as breast cancer, lung cancer, gastric cancer, and liver cancer [43–45] and autoimmune diseases such as related genes into primary miRNAs (pri-miRNAs), where miRNAs are several thousand nucleotides (nt) long [26–28]. multiple sclerosis, systemic lupus erythematosus, and ar- Subsequently, the microprocessing complex Drosha- thritis [46–48]. .e above studies indicated that miR-23b is DGCR8, consisting of the RNA binding protein DiGeorge mainly involved in a variety of physiological processes such syndrome critical region gene8 (DGCR8) and the ribonu- as cell proliferation, migration, and adhesion [49, 50]. clease type III RNase Drosha, splits the precursor miRNA (pre-miRNA), which forms the hairpin structure [29, 30]. 4. The Role of miR-23b in Cancer .is process is carried out in the nucleus. .en, in the cytoplasm, the RNA Dicer enzyme decomposed per-miRNA 4.1. Breast Cancer. miR-23b is a pathogenic gene in the into mature miRNA, and the miRNA was still in the double- course of the occurrence of breast tumors. Because miR-23b stranded state [29]. Finally, the double-stranded miRNA expression changes abnormally in breast cancer, it is con- combined with Argonaute2 (AGO2) to form RISC (RNA- sidered a biomarker for breast cancer development. .e induced silencing complex) [31]. One strand of the miRNA expression rate of miR-23b in breast cancer tissues was double strand is preserved in the RISC complex, while the signiﬁcantly higher than that in benign breast ﬁbroadeno- other strand is expelled from the complex and rapidly de- mas. .rough KEGG pathway enriching analysis, it is found grades [30]. In the cytoplasm, miRNAs exert various bio- that miR-23b is involved in the metabolism and cellular logical functions by RISC [32]. miRNAs processing and pathway of breast cancer, such as EGFR and c-Met signaling loading into RISC is performed by speciﬁc RNA-biding pathways [51, 52]. In addition, the function of miR-23b at proteins (RBPs), which exert cotranscriptional and post- the cellular and molecular level has also been extensively transcriptional regulation of miRNA transcription product studied. .e CRISPR/Cas9 system was able to knock out [33]. Moreover, a number of miRNAs can have diﬀerent miR-23b and miR-27b thoroughly; therefore, some re- nuclear functions independently of RISC [33]. searchers used this system to knock out the miR-23b gene in Journal of Oncology 3 defects of Tregs. .erefore, the treatment of autoimmune MCF-7 cells. .e results showed that the cell behaviors were changed, such as cell growth rate and colony formation, and liver disease aims to restore the suﬃcient number and function of Treg [64, 65]. signiﬁcantly decreased [53, 54]. Moreover, miR-23b ex- pression is regulated by multiple factors. A study shows that In hepatocellular carcinoma (HCC) cells, miR-23b the membrane receptor tyrosine kinase (HER2/neu) can possessed important functions [66]. miR-23b may possess a induce miR-23b by regulating its downstream transcription dual function of oncogenic and inhibitory eﬀect on the factor NF- B, promoting the growth of breast cancer cells tumor. Because the expression of miR-23b is detected in 125 [55]. On the other hand, miR-23b blockades tumor cell HCC patients, 48 of them were upregulated, and 77 were invasion by inhibiting the expression of B-lymphocyte-in- downregulated [67]. In Cao’s research, it was shown that the duced maturation protein-1 (Blimp1) [43, 56]. Cas/ErbB2 expression of miR-23b in HCC tissues was remarkably MCF10A.B2 represents invasive human mammary epithelial decreased, which was positively correlated with metastasis of HCC [44]. Intriguingly, body fat is also associated with the cells with characteristics of overexpression p130Cas and activation of ErbB2. miR-23b can directly reversely mediate progression of liver cancer. Compared with HCC patients with low body fat percentage, the study has found that serum Blimp1 and increase its level of expression [43]. exosomes of HCC patients with a high body fat ratio express a high level of miR-23b [68]. Besides, hepatocellular car- 4.2.LungCancer. miR-23b is identiﬁed to be related to lung cinoma cell line SMMC-7721 demonstrated that miR-23b cancer according to a variety of validation methods, in- could promote tumor cell growth by targeting suppression cluding PCR array, logistic regression, and receiver oper- of tumorigenicity 7 like (ST7L) [66]. Proline-rich tyrosine ating characteristics curve analyses; mir-23b is determined kinase 2 (PYK2) is a nonreceptor tyrosine kinase belonging to be closely related to the formation of lung cancer [57]. By to the adhesion-focused kinase family [69]. PYK2 plays an performing an MTT assay, it was demonstrated that, in the essential role in regulating cell proliferation and migration in H1838 lung cancer cell line, the overexpression of miR-23b various cancer cells [70, 71], and miR-23b inhibits the HCC signiﬁcantly improved cell viability. In H1437 and H1944 cell line MHCC97L by targeting Pyk2 [72]. lung cancer cell lines, inhibiting the expression of miR-23b signiﬁcantly reduced the ability of cell proliferation [45]. .e speciﬁc mechanisms of action indicate that, by increasing 4.4. Gastric Cancer. .e high expression of miR-23b, a the expression of miR-23b, it acts on myeloid leukemia 1 typical feature of gastric cancer, is believed to facilitate this short (Mcl-1S) gene to enhance the proliferation, migration, disease’s aggressive progression [73]. Moreover, miR-23b in and invasion ability of A549 cells [58]. Mcl-1S has a plasma expression is correlated with a poor prognosis of proapoptosis eﬀect, which is a short splicing variant of gastric cancer [74]. miR-23b is one of the critical factors in antiapoptosis protein Mcl-1 [59]. .is may be the main the initiation and progression of gastric cancer. By per- reason that miR-23b can promote the growth of lung cancer forming experiments in a gastric cancer xenograft mouse cells. A new study proved that kinectin1 antisense RNA 1 model and gastric cancer cells MKN-45 and AGS, results can (KTN1-AS1) is negatively correlated with miR-23b in identify that miR-23b could target programmed cell death NSCLC (non-small-cell lung cancer) cells, and the over- (PDCD4) and promote tumor growth [75]. Besides, it has expression of KTN1-AS1 can signiﬁcantly reduce the ex- demonstrated that miR-23b and long noncoding RNA, pression level of miR-23b. Administration of KTN1-AS1 can tumor suppressor candidate 7 (TUSC7), inhibited each restore the proliferation and growth of NSCLC cells [60]. other. Contrary to the eﬀect of miR-23b, TUSC7 suppressed KTN1-AS1 contributes to facilitating NSCLC progression by the growth of gastric cancer cells AGS and MKN-45 [76]. inhibiting miR-23b [60]. .e latest clinical data has shown that miR-23b encapsulated in the exosomes can also be used as a biomarker to predict the recurrence and prognosis of gastric cancer patients at 4.3. Liver Cancer. .ere is a critical relationship between diﬀerent stages [77]. liver cancer and immunity [61, 62]. .e liver acts as an .e mechanism of miR-23b in breast cancer, lung immune organ, maintaining immune homeostasis and cancer, liver cancer, and gastric cancer is shown in Figure 1. containing many immune cells, such as DC cells and T cells [61]. Tregs are an immunosuppressive subset of CD4+ T cells. Tregs have an important feature; that is, they have 5. The Role of miR-23b in Autoimmune Disease both activating and inhibitory receptors. Blocking activated receptors and/or stimulating inhibitory receptors shifts the 5.1. MS/EAE. Abnormal expression of a series of micro- balance to inhibiting Tregs, treating tumors and chronic in- RNAs can be used as potential therapeutic targets for EAE, fectious diseases. Furthermore, Tregs play a crucial role during assessed in the plasma and spinal cord tissue of EAE mice tumor development and progression by regulating other im- [78]. In addition to the dysregulation of miR-23b in the mune cells. Notably, Tregs work with neutrophils to reduce the tumor diseases mentioned above, miR-23b also reﬂected incidence of liver cancer [63]. On the contrary, the therapeutic abnormal expression in autoimmune diseases. .e analysis eﬀects of Treg can be achieved by blocking the inhibitory of a miRNA-microarray found that, with the aggravation of receptors or stimulating the activation receptors in auto- EAE, the expression of miR-23b gradually increased. .is immune diseases [62]. According to the reports, autoim- result is considered to be one of the biomarkers of the disease mune liver disease is related to the number and functional [79]. Moreover, several studies have reported that miR-23b 4 Journal of Oncology lung cancer breast cancer HER2 H1838 TNF-α H1437 H1944 Akt EGF apoptosis BT474 A549 Mcl-1S proliferation proliferation NSCLC Cas/ErbB2 invision migration MCF10A.B2 Blimp1 KTN1-AS1 miR-23b ST7L PDCD4 proliferation PYK2 apoptosis migration invasion TUSC7 migration growth MKN-45 invasion growth SMMC-7721 AGS MHCC97L gastric cancer liver cancer Figure 1: .e mechanism of miR-23b in cancers. (1) Breast cancer: HER2, EGF, and TNF-α promote the growth of BT474 cells by promoting the upregulation of miR-23b. Cas/ErbB2 MCF10A.B2 represents overexpression p130Cas with activation of ErbB2. miR-23b impairs Cas/ErbB2 MCF10A.B2 cell invasion by downmodulating Blimp1 expression. (2) Lung cancer: miR-23b promotes H1838, H1437, and H1944 lung cancer cell proliferation. It is beneﬁcial for the growth of A549 by Mcl-1S. In addition, KTN1-AS1 promotes NSCLC proliferation by inhibiting miR-23b. (3) Liver cancer: miR-23b boosts the proliferation of H1838, H1437, and H1944 lung cancer cell lines. It is useful for the expansion of A549 by Mcl-1S. Furthermore, KTN1-AS1 accelerates NSCLC proliferation by inhibiting miR-23b. (4) Gastric cancer: miR-23b modulates tumor growth by targeting PDCD4. Moreover, as a potential target of miR-23b, TUSC7 also regulates the growth of gastric cancer cells AGS and MKN-45. regulates autoimmune disease pathogenesis by targeting 5.2. RA. RA chronically damages the heart, skin, and diﬀerent protein molecules, such as TAB2, TAB3, IKK-α, many other organs, accompanied by pathological char- and CCL-7. acteristics of erosive changes in joint surfaces that lead to Bone marrow mesenchymal stem cells (BMSCs), adult the destruction of the joints [80]. Besides its speciﬁc pluripotent stem cells, exert the immunoregulatory role by expression in MS, miR-23b is also expressed explicitly in carrying miRNA. BMSCs combined with miR-23b had a arthritis. It is therefore considered to be a biomarker of better synergistic eﬀect and could eﬀectively alleviate EAE RA [47]. .e identiﬁcation of miR-23b expression shows downregulation in inﬂammatory lesions from RA indi- [46]. BMSC loading overexpression miR-23b inhibits .17 cell diﬀerentiation, blocks the secretion of inﬂammatory viduals and related mouse models compared with healthy factor IL-17, on the contrary promotes the secretion of controls [42]. It is well known that RA is more common in tumor growth factor-beta 1 (TGF-β1), and ultimately old age [81]. However, juvenile idiopathic arthritis will inhibits the development of EAE [46]. In addition to also occur in a high proportion, which is very detrimental analyzing the eﬀect of miR-23b on EAE veriﬁcation from to the growth of children [82]. .e study has shown that the perspective of inﬂammatory subset cells .17, the miR-23b helps in the diagnosis and monitoring of RA research focuses on the eﬀect of inﬂammatory chemokine [83]. miR-23b is negatively related to inﬂammation in RA CCL7. Similar to the eﬀect of miR-23b in .17 cells, miR- [47]. Similarly, the negative correlation between IL-17 23b inhibits .1 and .17 cells and diminishes the in- and miR-23b is veriﬁed in comparing RA patients and ﬁltration of encephalitogenic T cells into the central healthy subjects [42]. In addition, Zhu et al. found that (TAB2), TAB3, and nuclear factor k-B kinase subunit α nervous system contributing to halting EAE by binding with CCL7 in the 3′-UTR site [41]. In addition, miR-23b (IKK-α) were down-regulated after transfection of miR- could alleviate the severity of EAE by targeting TAB2, 23b in ﬁbroblast-like synovial cells (FLSs), which were TAB3, and IKK-α [42]. obtained from synovial joint tissues of individuals with Journal of Oncology 5 knee joint injury. [42]. .erefore, it is implied that miR- 23b can target TAB2, TAB3, and IKK-α to alleviate miR-23b disease. CCL7 5.3. SLE. SLE is an autoimmune disease in women with features of multiple tissues and systems [84]. Moreover, TAB2 TAB3 brain tissue is often the target organ of this disease. Due to the long-term and widespread existence of intracranial migration vascular inﬂammation, part of the gray matter shows is- chemia, infarction, atrophy, and several demyelinations of IKK-α white matter areas [85]. .e injury of the gray and white matter directly aﬀects nerve function and leads to abnormal clinical symptoms. .e incidence of SLE is increasing year by year, with facial erythema, joint pain, fever, and fatigue as the primary manifestations. Using the mouse model of SLE, the research has veriﬁed that the treatment of adipose-derived stem cells (ADSCs) can eﬀectively alleviate the progression Th17 of the disease. Speciﬁcally, it reduces the expression of in- ﬂammatory factor IL-17, which may be related to the Th1 upregulation of miR-23b [48]. Additionally, through RNA diﬀerential analysis of renal biopsy samples from several patients with SLE, it is found that miR-23b is downregulated EAE in the inﬂammatory sites of SLE patients [42]. Similar to RA, miR-23b also inhibited the development of SLE upon RA/SLE inhibiting TAB2, TAB3, and IKK-α [42]. All in all, the high expression of miR-23b will be helpful for the relief of SLE. Figure 2: .e mechanism of miR-23b in MS, RA, and SLE. IKK-α .e mechanism of action of miR-23b in EAE, RA, and could promote the expression of inﬂammatory factor NF-B, which contributes to the occurrence of autoimmune diseases RA, SLE is summarized in Figure 2. SLE, and MS/EAE. Additionally, miR-23b could alleviate these diseases by inhibiting TAB2 and TAB3, which are beneﬁcial for 6. Treatment IKK-α. Besides, the binding of miR-23b to CCL7 can inhibit the migration of inﬂammatory cells .1 and .17 and ultimately miRNAs are abnormally expressed in various pathological inhibit disease development. processes. Restoring miRNA normal levels might be regarded as a promising therapy. Up to date, miRNA inhibitors have human and mouse brains and later showed that this circRNA been frequently used in the study of miRNA function and could act as a sponge for miRNAs [99, 100]. For example, mechanism. It is common to use artiﬁcial inhibitors, in- circHIPK3 is the sponge of miR-558 inhibiting bladder cancer cluding anti-miRNA oligonucleotide (AMO) and miRNA development bothinvivo andinvitro [101]. Notably, miR-23b sponges [86]. AMO is a short-stranded RNA oligonucleotide sponge is also applied to liver cancer cells and glioma cells, that is complementary to natural miRNAs [87]. AMO has and the results show that it has a good eﬀect in inhibiting the been used in various cancers [88–91]. Artiﬁcial miRNA disease [102, 103]. In addition to the above methods for sponge is constructed by inserting tandemly arrayed miRNA regulating miRNA levels, RNA mimics can be used as well. sites into 3′-terminus (3′ 3′-UTRs) of a reporter gene [92]. miRNA mimics are double-stranded RNA molecules, which .is type of miRNA sponge is characterized by inductive and modulate miRNA level [25]. miRNA mimic is a strategy to stable expression, driven by the most potent promoters in restore miRNA function. Even viral vectors can transfect mammalian systems, such as U6 or cytomegalovirus (CMV) miRNA into cells, but they have genome integration and the [93]. MicroRNA (miRNA) sponges are transcripts with re- potential danger of immunogenicity [104]. For example, miR- peated miRNA antisense sequences that can sequester 125b-5p mimic has been demonstrated to inhibit acute liver miRNAs from the endogenous target, leading to miRNA injury in vivo [105]. .erefore, miRNA mimic does not in- translation inhibition or mRNA degradation to fail [94]. .e tegrate into the genome, making it a good prospect in disease microRNA sponge can play a role in cancer treatment. For treatment [104]. In conclusion, the AMO, sponge, and mimic example, there have been studies based on the bladder cancer of miR-23b can potentially treat cancers and autoimmune xenograft model of BALB/c nude mice, and lentivirus- diseases. transduced miR-130b/miR-494 sponge inhibits tumor growth [95]. Besides, the miRNA sponge also has excellent potential in the treatment of liver cancer. To be speciﬁc, miR-17-3p, 7. Conclusion miR-181b-5p, and miR-9 sponges all demonstrated the ability to inhibit the growth of liver cancer cells [96–98]. Interest- miR-23b is frequently upregulated in a variety of tumors and ingly, the team identiﬁed a circRNA that is highly expressed in human cancer cell lines and exerts a vital function in 6 Journal of Oncology process, it is inevitable that the expression of miR-23b is tumorigenesis. .e expression level of miR-23b is induced by the HER2/neu, EGF, TNF-α, and Blimp1, constitutively abnormal and undulatory during the occurrence of the disease. Regulating miR-23b to its normal level is a new activated in breast cancer [43, 55]. In studies on lung cancer cell lines and NSCLC cells, miR-23b has been shown to potential therapeutic strategy for treating related diseases. So promote cancer development. .erefore, miR-23b is a po- far, the application of miRNA sponges, AMOS, and mimics tential clinical pathologic marker in lung cancer [57]. In has provided favorable conditions for regulating abnormal addition, miR-23b can be used as a novel therapeutic target. miR-23b expression. Studies in liver cancer have shown that ST7L, as the direct target of miR-23b, plays a regulatory role in liver cancer cells Conflicts of Interest and can act as an oncogene [66]. Finally, for gastric cancer, miR-23b promotes tumor development by targeting PDCD4 .e authors declare that they have no conﬂicts of interest. [75]. It has been shown to antagonize TUSC7, a tumor inhibitor [76]. However, the regulatory role of miR-23b Authors’ Contributions looks paradox in diﬀerent cancer. In conclusion, miRNA- All authors listed have made substantial contributions to the 23b expression proﬁles diﬀer between disease states and normal tissue, and the abnormal regulation of miR-23b can work and have approved to publish it. be used as a warning for tumors in tumor studies. However, its regulatory eﬀects on a variety of proteins make it a very Acknowledgments challenging target for cancer therapy. In general, for tumors, .is study was supported by the Chinese National Natural miR-23b often has diﬀerent roles in divergent systems or Science Foundation (Grant nos. 31970771, 82071396, and environments. It is consistent with previous research il- 81771345), the Natural Science Foundation of Shaanxi lustrating that one of the frustrating aspects of microRNA Province, China (Grant nos. 2021ZDLSF03-09 and 2020SF- research is that individual microRNAs have opposite 314), and the Fundamental Research Funds for the Central functions in diﬀerent systems, suggesting that microRNA Universities (Grant nos. GK202007022, GK202105002, communication is environment-dependent [34]. Some ex- GK202006003, TD2020039Y, and 2020CSZL009). amples demonstrate that miR-125b is downregulated in various cancers such as hepatocellular carcinoma and breast cancer and overexpressed in colon cancer and hepatocellular References tumors [106]. Furthermore, future work should build on the [1] H. Sung, J. 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Publisher: Hindawi Publishing Corporation
Copyright: Copyright © 2021 Yu-Xin Guo et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
ISSN: 1687-8450
eISSN: 1687-8469
DOI: 10.1155/2021/6473038
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Abstract

Hindawi Journal of Oncology Volume 2021, Article ID 6473038, 9 pages https://doi.org/10.1155/2021/6473038 Review Article 1 2 1 1 3 Yu-Xin Guo , Na Wang , Wen-Cheng Wu , Cui-Qin Li , Rui-Heng Chen , 1 1 Yuan Zhang , and Xing Li National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest China, Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry (Shaanxi Normal University), 'e Ministry of Education, College of Life Sciences, Shaanxi Normal University, Xi’an, Shaanxi 710119, China Surgical Oncology Department, 'e First People’s Hospital of Tianshui, Tianshui, Gansu 741000, China 'e High School Aﬃliated to Shaanxi Normal University, Xi’an, Shaanxi 710119, China Correspondence should be addressed to Yuan Zhang; yuanzhang_bio@126.com and Xing Li; xingli_xian@126.com Received 27 May 2021; Accepted 18 October 2021; Published 3 November 2021 Academic Editor: Alessandro Granito Copyright © 2021 Yu-Xin Guo et al. .is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Short-stranded miRNAs are single-stranded RNA molecules involved in the regulation of gene expression. miRNAs are involved in a variety of cellular physiological processes, including cell proliferation, diﬀerentiation, and apoptosis. miR-23b have been identiﬁed to act both as oncogenes and as tumor suppressors. In addition, miR-23b is related to inﬂammation resistance to various autoimmune diseases and restrained inﬂammatory cell migration. .e characterization of the speciﬁc alterations in the patterns of miR-23b expression in cancer and autoimmune disease has great potential for identifying biomarkers for early disease diagnosis, as well as for potential therapeutic intervention in various diseases. In this review, we summarize the ever-expanding role of miR- 23b and its target genes in diﬀerent models and oﬀer insight into how this multifunctional miRNA modulates tumor cell proliferation and apoptosis or inﬂammatory cell activation, diﬀerentiation, and migration. divided into drug therapy and surgical treatment [7]. Drug 1. Introduction therapy refers to using drugs to destroy cancer cells, which is According to GLOBOCAN 2020, an assessment of cancer often used in clinical treatment. However, while killing morbidity and mortality, it is reported that the number of tumor cells, it will kill normal cells, so it often brings a series new cancer cases reached 19.3 million worldwide, and al- of side eﬀects, and chemotherapy does not have speciﬁcity most 10 million people died from cancer [1]. Moreover, for tumor tissue [8]. .us, most drug therapy has side eﬀects. breast cancer in women has overtaken lung cancer as the In addition, surgical treatment has adverse eﬀects such as primary cause of cancer incidence worldwide in 2020 [1, 2]. postoperative recurrence and slow healing. Importantly, .en, lung cancer is the second most frequently occurring their pathogenesis is also unclear [9]. .ese factors lead to cancer and the leading cause of cancer death [1]. Moreover, limited treatment options. .erefore, clarifying the speciﬁc changes in incidence and trends are closely related to the mechanism of the disease is of great signiﬁcance for the prevalence of tobacco [3, 4]. So, men are more likely to suﬀer treatment of the disease. from this disease. Among male cancers, liver cancer is also a Autoimmune disease refers to a disease in which the high incidence disease, ranking second in male mortality, body’s immune response to its antigen causes damage to its and the incidence of primary liver cancer has continued to own tissues [10]. Multiple sclerosis (MS) is an autoimmune rise since 2020 [4, 5]. Gastric cancer is a signiﬁcant disease demyelinating central nervous system (CNS) disease, in worldwide. Notably, in the United States, Canada, and the which immune cells inﬁltrate into the central nervous United Kingdom, the incidence of gastric cancer has in- system from the periphery, activate microglia and astrocytes, creased in both low- and high-risk young adults (younger and inhibit the diﬀerentiation of oligodendrocytes into ol- than 50 years) [6]. At present, the treatment of tumors can be igodendrocytes, resulting in pathological features such as 2 Journal of Oncology demyelination of myelin and axon [11, 12]. However, its MicroRNA regulation commonly occurs based on exact molecular mechanisms remain unclear. Besides, microRNA binding to the 3′ untranslated region (3′-UTR) of target mRNA [34]. MicroRNAs inhibit the expression of rheumatoid arthritis (RA), also a chronic autoimmune disease, aﬀects nearly 0.5%–1% of the population in the target genes by 3′-UTR combining with target RNAs [35]. world [13]. .e most common clinicopathological features .erefore, diﬀerent miRNA biological processes occur at of RA patients are cartilage degeneration and bone erosion diﬀerent sites in the cell, including RNA transcription, of large and small joints, leading to mobility diﬃculties and processing, transport, and RISC binding. Importantly, even disability in severe cases [14, 15]. Although there is miRNAs are critical for cell proliferation, diﬀerentiation, some genetic and environmental correlation, the speciﬁc and apoptosis [36]. miRNAs have been involved in many pathogenesis is not clear [16]. Systemic lupus eryth- cancers and neurodegenerative diseases, such as multiple ematosus (SLE) is also a chronic multisystem autoimmune sclerosis, Parkinson’s disease, and Alzheimer’s disease disorder. Although the cause of SLE is unknown, both [37, 38]. Overall, miRNAs play an essential part in the genetic and environmental elements are relevant to the occurrence and development of diseases [39]. disease mechanism [17]. Infection and environmental el- ements have been hypothesized to cause cell damage, 3. miR-23b Research Progress promote the exposure of autoantigens to the immune system, and cause B- and T-cell activation [18]. Indeed, .e miR-23b is due to the chromosomal region 9q22,32 clarifying the pathogenesis plays a critical role in the di- encoding mi-23b/27b/24-1 [23]. .e biogenetic process of agnosis and timely treatment of diseases. miR-23b is similar when miRNA is cut into miRNA double Small endogenous regulatory RNAs, also known as strand by Dicer enzyme-containing protein complex. One short-strand ribonucleic acid microRNAs (miRNAs), are strand is a passenger strand that will be degraded, and the critical posttranscriptional regulators of gene expression and other is miR-23b. miR-23b is involved in regulating normal were ﬁrst identiﬁed in C. elegans [19–21]. .ere are many physiological function, cell diﬀerentiation, and cellular kinds of miRNAs, among which miRNA-23b belongs to immunity [40]. .us, when the miR-23b homeostasis is miR-23b/27b/24-1 cluster [22]. miR-23b possessed regula- damaged, the normal physiological function of the cell will tory roles, especially in the development of cancer and also be aﬀected, and then diseases will occur. miR-23b can autonomic immune diseases [23]. In conclusion, this review induce a complex network of responses by directly targeting reveals miR-23b in various diseases, including cancer and multiple transcripts. To be speciﬁc, the changes of miR-23b autoimmune diseases, and its role in disease progression. expression were closely related to various transcription factors, such as TAB2, TAB3, NF-κB, tumor suppressor P53, estrogen receptor ER-α, mitogen-activated protein kinase 2. miRNA MAPK, activation protein AP-1, reactive oxygen species MicroRNA (miRNAs), which belonged to a category of ROS, and CCL7 [19, 41, 42]. It has been reported that miR- single-stranded RNA molecular, is not involved in coding 23b is closely related to the occurrence and development of a with a role in regulating gene expression [24, 25]. .e variety of diseases, including tumors and autoimmune formation of miRNA includes the multistage process. Firstly, diseases [23]. .is review summarized tumor-related dis- in the nucleus, RNA polymerase II or III transcripts miRNA- eases such as breast cancer, lung cancer, gastric cancer, and liver cancer [43–45] and autoimmune diseases such as related genes into primary miRNAs (pri-miRNAs), where miRNAs are several thousand nucleotides (nt) long [26–28]. multiple sclerosis, systemic lupus erythematosus, and ar- Subsequently, the microprocessing complex Drosha- thritis [46–48]. .e above studies indicated that miR-23b is DGCR8, consisting of the RNA binding protein DiGeorge mainly involved in a variety of physiological processes such syndrome critical region gene8 (DGCR8) and the ribonu- as cell proliferation, migration, and adhesion [49, 50]. clease type III RNase Drosha, splits the precursor miRNA (pre-miRNA), which forms the hairpin structure [29, 30]. 4. The Role of miR-23b in Cancer .is process is carried out in the nucleus. .en, in the cytoplasm, the RNA Dicer enzyme decomposed per-miRNA 4.1. Breast Cancer. miR-23b is a pathogenic gene in the into mature miRNA, and the miRNA was still in the double- course of the occurrence of breast tumors. Because miR-23b stranded state [29]. Finally, the double-stranded miRNA expression changes abnormally in breast cancer, it is con- combined with Argonaute2 (AGO2) to form RISC (RNA- sidered a biomarker for breast cancer development. .e induced silencing complex) [31]. One strand of the miRNA expression rate of miR-23b in breast cancer tissues was double strand is preserved in the RISC complex, while the signiﬁcantly higher than that in benign breast ﬁbroadeno- other strand is expelled from the complex and rapidly de- mas. .rough KEGG pathway enriching analysis, it is found grades [30]. In the cytoplasm, miRNAs exert various bio- that miR-23b is involved in the metabolism and cellular logical functions by RISC [32]. miRNAs processing and pathway of breast cancer, such as EGFR and c-Met signaling loading into RISC is performed by speciﬁc RNA-biding pathways [51, 52]. In addition, the function of miR-23b at proteins (RBPs), which exert cotranscriptional and post- the cellular and molecular level has also been extensively transcriptional regulation of miRNA transcription product studied. .e CRISPR/Cas9 system was able to knock out [33]. Moreover, a number of miRNAs can have diﬀerent miR-23b and miR-27b thoroughly; therefore, some re- nuclear functions independently of RISC [33]. searchers used this system to knock out the miR-23b gene in Journal of Oncology 3 defects of Tregs. .erefore, the treatment of autoimmune MCF-7 cells. .e results showed that the cell behaviors were changed, such as cell growth rate and colony formation, and liver disease aims to restore the suﬃcient number and function of Treg [64, 65]. signiﬁcantly decreased [53, 54]. Moreover, miR-23b ex- pression is regulated by multiple factors. A study shows that In hepatocellular carcinoma (HCC) cells, miR-23b the membrane receptor tyrosine kinase (HER2/neu) can possessed important functions [66]. miR-23b may possess a induce miR-23b by regulating its downstream transcription dual function of oncogenic and inhibitory eﬀect on the factor NF- B, promoting the growth of breast cancer cells tumor. Because the expression of miR-23b is detected in 125 [55]. On the other hand, miR-23b blockades tumor cell HCC patients, 48 of them were upregulated, and 77 were invasion by inhibiting the expression of B-lymphocyte-in- downregulated [67]. In Cao’s research, it was shown that the duced maturation protein-1 (Blimp1) [43, 56]. Cas/ErbB2 expression of miR-23b in HCC tissues was remarkably MCF10A.B2 represents invasive human mammary epithelial decreased, which was positively correlated with metastasis of HCC [44]. Intriguingly, body fat is also associated with the cells with characteristics of overexpression p130Cas and activation of ErbB2. miR-23b can directly reversely mediate progression of liver cancer. Compared with HCC patients with low body fat percentage, the study has found that serum Blimp1 and increase its level of expression [43]. exosomes of HCC patients with a high body fat ratio express a high level of miR-23b [68]. Besides, hepatocellular car- 4.2.LungCancer. miR-23b is identiﬁed to be related to lung cinoma cell line SMMC-7721 demonstrated that miR-23b cancer according to a variety of validation methods, in- could promote tumor cell growth by targeting suppression cluding PCR array, logistic regression, and receiver oper- of tumorigenicity 7 like (ST7L) [66]. Proline-rich tyrosine ating characteristics curve analyses; mir-23b is determined kinase 2 (PYK2) is a nonreceptor tyrosine kinase belonging to be closely related to the formation of lung cancer [57]. By to the adhesion-focused kinase family [69]. PYK2 plays an performing an MTT assay, it was demonstrated that, in the essential role in regulating cell proliferation and migration in H1838 lung cancer cell line, the overexpression of miR-23b various cancer cells [70, 71], and miR-23b inhibits the HCC signiﬁcantly improved cell viability. In H1437 and H1944 cell line MHCC97L by targeting Pyk2 [72]. lung cancer cell lines, inhibiting the expression of miR-23b signiﬁcantly reduced the ability of cell proliferation [45]. .e speciﬁc mechanisms of action indicate that, by increasing 4.4. Gastric Cancer. .e high expression of miR-23b, a the expression of miR-23b, it acts on myeloid leukemia 1 typical feature of gastric cancer, is believed to facilitate this short (Mcl-1S) gene to enhance the proliferation, migration, disease’s aggressive progression [73]. Moreover, miR-23b in and invasion ability of A549 cells [58]. Mcl-1S has a plasma expression is correlated with a poor prognosis of proapoptosis eﬀect, which is a short splicing variant of gastric cancer [74]. miR-23b is one of the critical factors in antiapoptosis protein Mcl-1 [59]. .is may be the main the initiation and progression of gastric cancer. By per- reason that miR-23b can promote the growth of lung cancer forming experiments in a gastric cancer xenograft mouse cells. A new study proved that kinectin1 antisense RNA 1 model and gastric cancer cells MKN-45 and AGS, results can (KTN1-AS1) is negatively correlated with miR-23b in identify that miR-23b could target programmed cell death NSCLC (non-small-cell lung cancer) cells, and the over- (PDCD4) and promote tumor growth [75]. Besides, it has expression of KTN1-AS1 can signiﬁcantly reduce the ex- demonstrated that miR-23b and long noncoding RNA, pression level of miR-23b. Administration of KTN1-AS1 can tumor suppressor candidate 7 (TUSC7), inhibited each restore the proliferation and growth of NSCLC cells [60]. other. Contrary to the eﬀect of miR-23b, TUSC7 suppressed KTN1-AS1 contributes to facilitating NSCLC progression by the growth of gastric cancer cells AGS and MKN-45 [76]. inhibiting miR-23b [60]. .e latest clinical data has shown that miR-23b encapsulated in the exosomes can also be used as a biomarker to predict the recurrence and prognosis of gastric cancer patients at 4.3. Liver Cancer. .ere is a critical relationship between diﬀerent stages [77]. liver cancer and immunity [61, 62]. .e liver acts as an .e mechanism of miR-23b in breast cancer, lung immune organ, maintaining immune homeostasis and cancer, liver cancer, and gastric cancer is shown in Figure 1. containing many immune cells, such as DC cells and T cells [61]. Tregs are an immunosuppressive subset of CD4+ T cells. Tregs have an important feature; that is, they have 5. The Role of miR-23b in Autoimmune Disease both activating and inhibitory receptors. Blocking activated receptors and/or stimulating inhibitory receptors shifts the 5.1. MS/EAE. Abnormal expression of a series of micro- balance to inhibiting Tregs, treating tumors and chronic in- RNAs can be used as potential therapeutic targets for EAE, fectious diseases. Furthermore, Tregs play a crucial role during assessed in the plasma and spinal cord tissue of EAE mice tumor development and progression by regulating other im- [78]. In addition to the dysregulation of miR-23b in the mune cells. Notably, Tregs work with neutrophils to reduce the tumor diseases mentioned above, miR-23b also reﬂected incidence of liver cancer [63]. On the contrary, the therapeutic abnormal expression in autoimmune diseases. .e analysis eﬀects of Treg can be achieved by blocking the inhibitory of a miRNA-microarray found that, with the aggravation of receptors or stimulating the activation receptors in auto- EAE, the expression of miR-23b gradually increased. .is immune diseases [62]. According to the reports, autoim- result is considered to be one of the biomarkers of the disease mune liver disease is related to the number and functional [79]. Moreover, several studies have reported that miR-23b 4 Journal of Oncology lung cancer breast cancer HER2 H1838 TNF-α H1437 H1944 Akt EGF apoptosis BT474 A549 Mcl-1S proliferation proliferation NSCLC Cas/ErbB2 invision migration MCF10A.B2 Blimp1 KTN1-AS1 miR-23b ST7L PDCD4 proliferation PYK2 apoptosis migration invasion TUSC7 migration growth MKN-45 invasion growth SMMC-7721 AGS MHCC97L gastric cancer liver cancer Figure 1: .e mechanism of miR-23b in cancers. (1) Breast cancer: HER2, EGF, and TNF-α promote the growth of BT474 cells by promoting the upregulation of miR-23b. Cas/ErbB2 MCF10A.B2 represents overexpression p130Cas with activation of ErbB2. miR-23b impairs Cas/ErbB2 MCF10A.B2 cell invasion by downmodulating Blimp1 expression. (2) Lung cancer: miR-23b promotes H1838, H1437, and H1944 lung cancer cell proliferation. It is beneﬁcial for the growth of A549 by Mcl-1S. In addition, KTN1-AS1 promotes NSCLC proliferation by inhibiting miR-23b. (3) Liver cancer: miR-23b boosts the proliferation of H1838, H1437, and H1944 lung cancer cell lines. It is useful for the expansion of A549 by Mcl-1S. Furthermore, KTN1-AS1 accelerates NSCLC proliferation by inhibiting miR-23b. (4) Gastric cancer: miR-23b modulates tumor growth by targeting PDCD4. Moreover, as a potential target of miR-23b, TUSC7 also regulates the growth of gastric cancer cells AGS and MKN-45. regulates autoimmune disease pathogenesis by targeting 5.2. RA. RA chronically damages the heart, skin, and diﬀerent protein molecules, such as TAB2, TAB3, IKK-α, many other organs, accompanied by pathological char- and CCL-7. acteristics of erosive changes in joint surfaces that lead to Bone marrow mesenchymal stem cells (BMSCs), adult the destruction of the joints [80]. Besides its speciﬁc pluripotent stem cells, exert the immunoregulatory role by expression in MS, miR-23b is also expressed explicitly in carrying miRNA. BMSCs combined with miR-23b had a arthritis. It is therefore considered to be a biomarker of better synergistic eﬀect and could eﬀectively alleviate EAE RA [47]. .e identiﬁcation of miR-23b expression shows downregulation in inﬂammatory lesions from RA indi- [46]. BMSC loading overexpression miR-23b inhibits .17 cell diﬀerentiation, blocks the secretion of inﬂammatory viduals and related mouse models compared with healthy factor IL-17, on the contrary promotes the secretion of controls [42]. It is well known that RA is more common in tumor growth factor-beta 1 (TGF-β1), and ultimately old age [81]. However, juvenile idiopathic arthritis will inhibits the development of EAE [46]. In addition to also occur in a high proportion, which is very detrimental analyzing the eﬀect of miR-23b on EAE veriﬁcation from to the growth of children [82]. .e study has shown that the perspective of inﬂammatory subset cells .17, the miR-23b helps in the diagnosis and monitoring of RA research focuses on the eﬀect of inﬂammatory chemokine [83]. miR-23b is negatively related to inﬂammation in RA CCL7. Similar to the eﬀect of miR-23b in .17 cells, miR- [47]. Similarly, the negative correlation between IL-17 23b inhibits .1 and .17 cells and diminishes the in- and miR-23b is veriﬁed in comparing RA patients and ﬁltration of encephalitogenic T cells into the central healthy subjects [42]. In addition, Zhu et al. found that (TAB2), TAB3, and nuclear factor k-B kinase subunit α nervous system contributing to halting EAE by binding with CCL7 in the 3′-UTR site [41]. In addition, miR-23b (IKK-α) were down-regulated after transfection of miR- could alleviate the severity of EAE by targeting TAB2, 23b in ﬁbroblast-like synovial cells (FLSs), which were TAB3, and IKK-α [42]. obtained from synovial joint tissues of individuals with Journal of Oncology 5 knee joint injury. [42]. .erefore, it is implied that miR- 23b can target TAB2, TAB3, and IKK-α to alleviate miR-23b disease. CCL7 5.3. SLE. SLE is an autoimmune disease in women with features of multiple tissues and systems [84]. Moreover, TAB2 TAB3 brain tissue is often the target organ of this disease. Due to the long-term and widespread existence of intracranial migration vascular inﬂammation, part of the gray matter shows is- chemia, infarction, atrophy, and several demyelinations of IKK-α white matter areas [85]. .e injury of the gray and white matter directly aﬀects nerve function and leads to abnormal clinical symptoms. .e incidence of SLE is increasing year by year, with facial erythema, joint pain, fever, and fatigue as the primary manifestations. Using the mouse model of SLE, the research has veriﬁed that the treatment of adipose-derived stem cells (ADSCs) can eﬀectively alleviate the progression Th17 of the disease. Speciﬁcally, it reduces the expression of in- ﬂammatory factor IL-17, which may be related to the Th1 upregulation of miR-23b [48]. Additionally, through RNA diﬀerential analysis of renal biopsy samples from several patients with SLE, it is found that miR-23b is downregulated EAE in the inﬂammatory sites of SLE patients [42]. Similar to RA, miR-23b also inhibited the development of SLE upon RA/SLE inhibiting TAB2, TAB3, and IKK-α [42]. All in all, the high expression of miR-23b will be helpful for the relief of SLE. Figure 2: .e mechanism of miR-23b in MS, RA, and SLE. IKK-α .e mechanism of action of miR-23b in EAE, RA, and could promote the expression of inﬂammatory factor NF-B, which contributes to the occurrence of autoimmune diseases RA, SLE is summarized in Figure 2. SLE, and MS/EAE. Additionally, miR-23b could alleviate these diseases by inhibiting TAB2 and TAB3, which are beneﬁcial for 6. Treatment IKK-α. Besides, the binding of miR-23b to CCL7 can inhibit the migration of inﬂammatory cells .1 and .17 and ultimately miRNAs are abnormally expressed in various pathological inhibit disease development. processes. Restoring miRNA normal levels might be regarded as a promising therapy. Up to date, miRNA inhibitors have human and mouse brains and later showed that this circRNA been frequently used in the study of miRNA function and could act as a sponge for miRNAs [99, 100]. For example, mechanism. It is common to use artiﬁcial inhibitors, in- circHIPK3 is the sponge of miR-558 inhibiting bladder cancer cluding anti-miRNA oligonucleotide (AMO) and miRNA development bothinvivo andinvitro [101]. Notably, miR-23b sponges [86]. AMO is a short-stranded RNA oligonucleotide sponge is also applied to liver cancer cells and glioma cells, that is complementary to natural miRNAs [87]. AMO has and the results show that it has a good eﬀect in inhibiting the been used in various cancers [88–91]. Artiﬁcial miRNA disease [102, 103]. In addition to the above methods for sponge is constructed by inserting tandemly arrayed miRNA regulating miRNA levels, RNA mimics can be used as well. sites into 3′-terminus (3′ 3′-UTRs) of a reporter gene [92]. miRNA mimics are double-stranded RNA molecules, which .is type of miRNA sponge is characterized by inductive and modulate miRNA level [25]. miRNA mimic is a strategy to stable expression, driven by the most potent promoters in restore miRNA function. Even viral vectors can transfect mammalian systems, such as U6 or cytomegalovirus (CMV) miRNA into cells, but they have genome integration and the [93]. MicroRNA (miRNA) sponges are transcripts with re- potential danger of immunogenicity [104]. For example, miR- peated miRNA antisense sequences that can sequester 125b-5p mimic has been demonstrated to inhibit acute liver miRNAs from the endogenous target, leading to miRNA injury in vivo [105]. .erefore, miRNA mimic does not in- translation inhibition or mRNA degradation to fail [94]. .e tegrate into the genome, making it a good prospect in disease microRNA sponge can play a role in cancer treatment. For treatment [104]. In conclusion, the AMO, sponge, and mimic example, there have been studies based on the bladder cancer of miR-23b can potentially treat cancers and autoimmune xenograft model of BALB/c nude mice, and lentivirus- diseases. transduced miR-130b/miR-494 sponge inhibits tumor growth [95]. Besides, the miRNA sponge also has excellent potential in the treatment of liver cancer. To be speciﬁc, miR-17-3p, 7. Conclusion miR-181b-5p, and miR-9 sponges all demonstrated the ability to inhibit the growth of liver cancer cells [96–98]. Interest- miR-23b is frequently upregulated in a variety of tumors and ingly, the team identiﬁed a circRNA that is highly expressed in human cancer cell lines and exerts a vital function in 6 Journal of Oncology process, it is inevitable that the expression of miR-23b is tumorigenesis. .e expression level of miR-23b is induced by the HER2/neu, EGF, TNF-α, and Blimp1, constitutively abnormal and undulatory during the occurrence of the disease. Regulating miR-23b to its normal level is a new activated in breast cancer [43, 55]. In studies on lung cancer cell lines and NSCLC cells, miR-23b has been shown to potential therapeutic strategy for treating related diseases. So promote cancer development. .erefore, miR-23b is a po- far, the application of miRNA sponges, AMOS, and mimics tential clinical pathologic marker in lung cancer [57]. In has provided favorable conditions for regulating abnormal addition, miR-23b can be used as a novel therapeutic target. miR-23b expression. Studies in liver cancer have shown that ST7L, as the direct target of miR-23b, plays a regulatory role in liver cancer cells Conflicts of Interest and can act as an oncogene [66]. Finally, for gastric cancer, miR-23b promotes tumor development by targeting PDCD4 .e authors declare that they have no conﬂicts of interest. [75]. It has been shown to antagonize TUSC7, a tumor inhibitor [76]. However, the regulatory role of miR-23b Authors’ Contributions looks paradox in diﬀerent cancer. In conclusion, miRNA- All authors listed have made substantial contributions to the 23b expression proﬁles diﬀer between disease states and normal tissue, and the abnormal regulation of miR-23b can work and have approved to publish it. be used as a warning for tumors in tumor studies. However, its regulatory eﬀects on a variety of proteins make it a very Acknowledgments challenging target for cancer therapy. In general, for tumors, .is study was supported by the Chinese National Natural miR-23b often has diﬀerent roles in divergent systems or Science Foundation (Grant nos. 31970771, 82071396, and environments. It is consistent with previous research il- 81771345), the Natural Science Foundation of Shaanxi lustrating that one of the frustrating aspects of microRNA Province, China (Grant nos. 2021ZDLSF03-09 and 2020SF- research is that individual microRNAs have opposite 314), and the Fundamental Research Funds for the Central functions in diﬀerent systems, suggesting that microRNA Universities (Grant nos. GK202007022, GK202105002, communication is environment-dependent [34]. Some ex- GK202006003, TD2020039Y, and 2020CSZL009). amples demonstrate that miR-125b is downregulated in various cancers such as hepatocellular carcinoma and breast cancer and overexpressed in colon cancer and hepatocellular References tumors [106]. Furthermore, future work should build on the [1] H. Sung, J. 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Published: Nov 3, 2021

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The Role of miR-23b in Cancer and Autoimmune Disease

The Role of miR-23b in Cancer and Autoimmune Disease

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The Role of miR-23b in Cancer and Autoimmune Disease

The Role of miR-23b in Cancer and Autoimmune Disease

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