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

doi:10.1016/j.bbagrm.2018.06.003

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

Biochim Biophys Acta Gene Regul Mech. 2018 Jun 20;1861(7):603-612. doi: 10.1016/j.bbagrm.2018.06.003. Online ahead of print.

Authors

Eunsun Jung¹, Youngmo Seong², Bohyun Jeon¹, Young-Soo Kwon³, Hoseok Song⁴

Affiliations

¹ Department of Biomedical Sciences, College of Medicine, Korea University, Seoul 02841, Republic of Korea.
² Department of Bioscience & Biotechnology, Sejong University, Seoul 05006, Republic of Korea.
³ Department of Bioscience & Biotechnology, Sejong University, Seoul 05006, Republic of Korea. Electronic address: yngskwon@sejong.ac.kr.
⁴ Department of Biomedical Sciences, College of Medicine, Korea University, Seoul 02841, Republic of Korea. Electronic address: hoseoksong@korea.ac.kr.

PMID: 29935344
DOI: 10.1016/j.bbagrm.2018.06.003

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.

Keywords: CrossLinking ImmunoPrecipitation; Poly-A tail; RNA stability; miR-17-92 cluster; microRNA.