MicroRNAs of miR-17-92 cluster increase gene expression by targeting mRNA-destabilization pathways

Eunsun Jung, Youngmo Seong, Bohyun Jeon, Young Soo Kwon, Hoseok Song

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

MicroRNAs (miRNAs) of the miR-17-92 cluster are overexpressed in human cancers, and their enforced expression is tumorigenic in mouse models. A number of genes are reported to be targets of these miRNAs and are implicated in their tumorigenic potential. However, the mode of action by miRNAs suggests that global analysis of their targets is required to understand their cellular roles. In this study, we globally analyzed AGO2-bound mRNAs and found that the miR-17-92 miRNAs coherently repress multiple targets involved in the destabilization of mRNA. While the miRNAs repress the expression of their targets, they increase stability and lengthen the poly-A tails of non-target mRNAs. Furthermore, the expression of BTG3, TOB1, CSNK1A1 and ANKRD52 is negatively correlated with the expression of the miR-17-92 cluster in cancer cell lines. Our results suggest that the miR-17-92 miRNAs promote tumorigenesis not only by repression of key regulators, but also by posttranscriptional increases of global gene expression.

Original languageEnglish
Pages (from-to)603-612
Number of pages10
JournalBiochimica et Biophysica Acta - Gene Regulatory Mechanisms
Volume1861
Issue number7
DOIs
Publication statusPublished - 2018 Jul 1

Keywords

  • CrossLinking ImmunoPrecipitation
  • microRNA
  • miR-17-92 cluster
  • Poly-A tail
  • RNA stability

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics

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