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Cross-Talk Between circRNAs and mRNAs Modulates MiRNA-mediated Circuits and Affects Melanoma Plasticity

Cross-Talk Between circRNAs and mRNAs Modulates MiRNA-mediated Circuits and Affects Melanoma... CircularRNAs (circRNAs) are non-coding RNAs which compete for microRNA (miRNA) binding, influencing the abundance and stability of other RNA species. Herein we have investigated the effect of circRNAs on the mir200-ZEB1 feedback loop in relationship with the aggressiveness of human melanoma cells. We first compared the level of expression of key factors in the mir200-ZEB1 feedback loop in primary human melanoma cells compared with their matching metastatic one and found a correlation between the aggressiveness of the cells and the level of expression of ZEB1 and SNAI1. We also analyzed factors in the mir200-ZEB1 feedback loop, including circZEB1, during the phenotypic switching of human melanoma cells. Our results showed a correlation between the level of ZEB1 and SNAI1 and the fraction of cancer stem cells in the population. The level of circZEB1 was, however, consistently high during the entire phenotypic transformation. To understand this result we propose a mathematical model of the regulatory circuit. According to the model, the experimental observations can be explained by the presence of a back-splicing factor limiting circRNA production. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Cancer Microenvironment Springer Journals

Cross-Talk Between circRNAs and mRNAs Modulates MiRNA-mediated Circuits and Affects Melanoma Plasticity

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Publisher
Springer Journals
Copyright
Copyright © 2019 by Springer Nature B.V.
Subject
Biomedicine; Cancer Research; Oncology; Immunology; Cell Biology; Biochemistry, general; Biomedicine, general
ISSN
1875-2292
eISSN
1875-2284
DOI
10.1007/s12307-019-00230-4
Publisher site
See Article on Publisher Site

Abstract

CircularRNAs (circRNAs) are non-coding RNAs which compete for microRNA (miRNA) binding, influencing the abundance and stability of other RNA species. Herein we have investigated the effect of circRNAs on the mir200-ZEB1 feedback loop in relationship with the aggressiveness of human melanoma cells. We first compared the level of expression of key factors in the mir200-ZEB1 feedback loop in primary human melanoma cells compared with their matching metastatic one and found a correlation between the aggressiveness of the cells and the level of expression of ZEB1 and SNAI1. We also analyzed factors in the mir200-ZEB1 feedback loop, including circZEB1, during the phenotypic switching of human melanoma cells. Our results showed a correlation between the level of ZEB1 and SNAI1 and the fraction of cancer stem cells in the population. The level of circZEB1 was, however, consistently high during the entire phenotypic transformation. To understand this result we propose a mathematical model of the regulatory circuit. According to the model, the experimental observations can be explained by the presence of a back-splicing factor limiting circRNA production.

Journal

Cancer MicroenvironmentSpringer Journals

Published: Nov 16, 2019

References