Interplay between ceRNA and Epigenetic Control of microRNA: Modelling Approaches with Application to the Role of Estrogen in Ovarian Cancer

Tzy Wei Huang, Frank H.C. Cheng, Ching Cher Sanders Yan, Yu Ming Chuang, Chien Hong Cho, Hung Cheng Lai, Shih Feng Shieh, Michael W.Y. Chan, Je Chiang Tsai*

*此作品的通信作者

研究成果: 雜誌貢獻期刊論文同行評審

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摘要

MicroRNAs (miRNAs) play an important role in gene regulation by degradation or translational inhibition of the targeted mRNAs. It has been experimentally shown that the way miRNAs interact with their targets can be used to explain the indirect interactions among their targets, i.e., competing endogenous RNA (ceRNA). However, whether the protein translated from the targeted mRNAs can play any role in this ceRNA network has not been explored. Here we propose a deterministic model to demonstrate that in a network of one miRNA interacting with multiple-targeted mRNAs, the competition between miRNA-targeted mRNAs is not sufficient for the significant change of those targeted mRNA levels, while dramatic changes of these miRNA-targeted mRNAs require transcriptional inhibition of miRNA by its target proteins. When applied to estrogen receptor signaling pathways, the miR-193a targets E2F6 (a target of estrogen receptor), c-KIT (a marker for cancer stemness), and PBX1 (a transcriptional activator for immunosuppressive cytokine, IL-10) in ovarian cancer, such that epigenetic silencing of miR-193a by E2F6 protein is required for the significant change of c-KIT and PBX1 mRNA level for cancer stemness and immunoevasion, respectively, in ovarian cancer carcinogenesis.

原文英語
文章編號2277
期刊International journal of molecular sciences
23
發行號4
DOIs
出版狀態已發佈 - 2022 2月 1
對外發佈

ASJC Scopus subject areas

  • 分子生物學
  • 光譜
  • 催化
  • 無機化學
  • 電腦科學應用
  • 物理與理論化學
  • 有機化學

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