Investigating the epi-miRNome: identification of epi-miRNAs using transfection experiments

Epigenomics. 2019 Nov;11(14):1581-1599. doi: 10.2217/epi-2019-0050. Epub 2019 Nov 6.

Abstract

Aim: Growing evidence shows a strong interplay between post-transcriptional regulation, mediated by miRNAs (miRs) and epigenetic regulation. Nevertheless, the number of experimentally validated miRs (called epi-miRs) involved in these regulatory circuitries is still very small. Material & methods: We propose a pipeline to prioritize candidate epi-miRs and to identify potential epigenetic interactors of any given miR starting from miR transfection experiment datasets. Results & conclusion: We identified 34 candidate epi-miRs: 19 of them are known epi-miRs, while 15 are new. Moreover, using an in-house generated gene expression dataset, we experimentally proved that a component of the polycomb-repressive complex 2, the histone methyltransferase enhancer of zeste homolog 2 (EZH2), interacts with miR-214, a well-known prometastatic miR in melanoma and breast cancer, highlighting a miR-214-EZH2 regulatory axis potentially relevant in tumor progression.

Keywords: EZH2; epi-miRNA; epigenetic; feedback loop; miR-138; miR-145; miR-214; miR-31; miRs; polycomb complex; tumor progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / genetics
  • Cell Line, Tumor
  • Enhancer of Zeste Homolog 2 Protein / genetics
  • Epigenesis, Genetic / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Melanoma / genetics
  • MicroRNAs / genetics*
  • Polycomb Repressive Complex 2 / genetics
  • Transfection / methods

Substances

  • MicroRNAs
  • Enhancer of Zeste Homolog 2 Protein
  • Polycomb Repressive Complex 2