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UBE2T regulates FANCI monoubiquitination to promote NSCLC progression by activating EMT

UBE2T regulates FANCI monoubiquitination to promote NSCLC progression by activating EMT Fanconi anemia complementation group I (FANCI) is a critical protein for maintaining DNA stability. However, the exact role of FANCI in tumors remains to be elucidated. The present study aimed to explore the role and potential mechanism of action of FANCI in non‑small cell lung cancer (NSCLC). To quantify the expression levels of FANCI and ubiquitin‑conjugating enzyme E2T (UBE2T) in NSCLC tissues, reverse‑transcription quantitative PCR and western blotting were employed. Cell Counting Kit‑8, wound healing and Transwell assays along with flow cytometry analysis and tumor xenograft were used to investigate the biological effects of FANCI in NSCLC <em>in vitro</em> and <em>in vivo</em>. The binding of FANCI with UBE2T was confirmed using a co‑immunoprecipitation assay. Epithelial‑to‑mesenchymal transition (EMT) protein markers were quantified via western blotting. The results showed that FANCI expression level was higher in NSCLC tumor tissues, compared with adjacent tissues. In A549 and H1299 cells, knockdown of FANCI inhibited cell proliferation, migration, invasion, cell cycle and EMT <em>in vitro</em>. Tumor growth was repressed <em>in vitro</em>, upon downregulation of FANCI expression. UBE2T was observed to directly bind to FANCI and regulate its monoubiquitination. Overexpression of UBE2T reversed the effects induced by FANCI knockdown in NSCLC cells. Furthermore, it was noted that FANCI interacted with WD repeat domain 48 (WDR48). Overexpression of WDR48 reversed the effects of FANCI on cell proliferation, migration and EMT. In conclusion, FANCI was identified to be a putative oncogene in NSCLC, wherein FANCI was monouniubiquitinated by UBE2T to regulate cell growth, migration and EMT through WDR48. The findings suggested that FANCI could be used as a prognostic biomarker and therapeutic target for NSCLC. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Oncology Reports Spandidos Publications

UBE2T regulates FANCI monoubiquitination to promote NSCLC progression by activating EMT

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References (47)

  • Chen (2016)

    115

    CA Cancer J Clin, 66

  • Longerich (2009)

    23182

    J Biol Chem, 284

  • Wu (2020)

    e18543

    Medicine (Baltimore), 99

  • Engel (2019)

    420

    Front Oncol, 9

  • Sun (2020)

    222

    J Exp Clin Cancer Res, 39

  • Beck (2011)

    549

    Mol Syst Biol, 7

  • Thiery (2003)

    740

    Curr Opin Cell Biol, 15

  • Zhang (2016)

    1134

    Cell Cycle, 15

  • Del Re (2019)

    3951

    Int J Mol Sci, 20

  • Zhu (2021)

    374

    J Transl Med, 19

  • Wang (2021)

    300

    Nat Struct Mol Biol, 28

  • Kelaidi (2019)

    612

    J Pediatr Hematol Oncol, 41

  • Livak (2001)

    402

    Methods, 25

  • Giaj-Levra (2020)

    387

    Expert Rev Anticancer Ther, 20

  • Ueki (2009)

    8752

    Cancer Res, 69

  • Rozelle (2021)

    1897

    Nat Commun, 12

  • Yang (2020)

    1033

    Hum Mutat, 41

  • Nepal (2017)

    1804

    Int J Mol Sci, 18

  • Smogorzewska (2007)

    289

    Cell, 129

  • Yin (2020)

    121

    Cancer Lett, 494

  • Xie (2019)

    e7408

    PeerJ, 7

  • Lioulia (2022)

    1694

    Mol Oncol, 16

  • Machida (2006)

    589

    Mol Cell, 23

  • Sondalle (2019)

    2561

    Proc Natl Acad Sci USA, 116

  • Zhang (2019)

    347

    Cancer Gene Ther, 26

  • Liu (2017)

    20

    Biochem Biophys Res Commun, 493

  • Han (2021)

    320

    Cell Cycle, 20

  • Cao (2018)

    1483

    Ann Thorac Surg, 105

  • Siegel (2022)

    7

    CA Cancer J Clin, 72

  • Wang (2018)

    418

    Cell Death Dis, 9

  • Hiley (2016)

    1002

    Lancet, 388

  • Doval (2019)

    S23

    Indian J Cancer, 56

  • Sato (2012)

    4553

    Nucleic Acids Res, 40

  • Zheng (2020)

    451

    Onco Targets Ther, 13

  • Zhao (2017)

    2145

    Cell Physiol Biochem, 42

  • Oka (2015)

    1385

    EMBO J, 34

  • Bray (2018)

    394

    CA Cancer J Clin, 68

  • Meetei (2003)

    165

    Nat Genet, 35

  • Zhu (2020)

    44

    Oncol Lett, 20

  • Hay (1995)

    8

    Acta Anat (Basel), 154

  • Dong (2015)

    32

    Hum Genomics, 9

  • Joo (2011)

    312

    Science, 333

  • Ceccaldi (2016)

    337

    Nat Rev Mol Cell Biol, 17

  • Kottemann (2013)

    356

    Nature, 493

  • van Twest (2017)

    247

    Mol Cell, 65

  • Katsuki (2016)

    T19

    Endocr Relat Cancer, 23

  • Paulo (2018)

    e1007355

    PLoS Genet, 14

Publisher
Spandidos Publications
Copyright
Copyright © 2022 Spandidos Publications
ISSN
1021-335X
DOI
10.3892/or.2022.8350

Abstract

Fanconi anemia complementation group I (FANCI) is a critical protein for maintaining DNA stability. However, the exact role of FANCI in tumors remains to be elucidated. The present study aimed to explore the role and potential mechanism of action of FANCI in non‑small cell lung cancer (NSCLC). To quantify the expression levels of FANCI and ubiquitin‑conjugating enzyme E2T (UBE2T) in NSCLC tissues, reverse‑transcription quantitative PCR and western blotting were employed. Cell Counting Kit‑8, wound healing and Transwell assays along with flow cytometry analysis and tumor xenograft were used to investigate the biological effects of FANCI in NSCLC <em>in vitro</em> and <em>in vivo</em>. The binding of FANCI with UBE2T was confirmed using a co‑immunoprecipitation assay. Epithelial‑to‑mesenchymal transition (EMT) protein markers were quantified via western blotting. The results showed that FANCI expression level was higher in NSCLC tumor tissues, compared with adjacent tissues. In A549 and H1299 cells, knockdown of FANCI inhibited cell proliferation, migration, invasion, cell cycle and EMT <em>in vitro</em>. Tumor growth was repressed <em>in vitro</em>, upon downregulation of FANCI expression. UBE2T was observed to directly bind to FANCI and regulate its monoubiquitination. Overexpression of UBE2T reversed the effects induced by FANCI knockdown in NSCLC cells. Furthermore, it was noted that FANCI interacted with WD repeat domain 48 (WDR48). Overexpression of WDR48 reversed the effects of FANCI on cell proliferation, migration and EMT. In conclusion, FANCI was identified to be a putative oncogene in NSCLC, wherein FANCI was monouniubiquitinated by UBE2T to regulate cell growth, migration and EMT through WDR48. The findings suggested that FANCI could be used as a prognostic biomarker and therapeutic target for NSCLC.

Journal

Oncology ReportsSpandidos Publications

Published: Aug 15, 2022

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