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.
|Number of pages
|Biochimica et Biophysica Acta - Gene Regulatory Mechanisms
|Published - 2018 Jul
Bibliographical noteFunding Information:
This work was supported by the Ministry of Education, Science and Technology through the National Research Foundation of Korea [ NRF-2011-0024962 and NRF-2015R1D1A1A01060145 to Y.-S.K.; 2014R1A1A2058610 to H.S.], and Ministry of Health and Welfare [ HI15C2835 to H.S.].
© 2018 Elsevier B.V.
- CrossLinking ImmunoPrecipitation
- Poly-A tail
- RNA stability
- miR-17-92 cluster
ASJC Scopus subject areas
- Structural Biology
- Molecular Biology