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

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Article number2277
JournalInternational journal of molecular sciences
Volume23
Issue number4
DOIs
Publication statusPublished - Feb 1 2022

Keywords

  • ceRNA
  • Deterministic model
  • Epigenetics
  • microRNA
  • Ovarian cancer
  • Target-translated protein

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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