JARID 1B expression and its function in DNA damage repair are tightly regulated by mi RNA s in breast cancer release_zmgbieatxjesxanwnlxmtj6wra

by Ivano Mocavini, Simone Pippa, Valerio Licursi, Paola Paci, Daniela Trisciuoglio, Cecilia Mannironi, Carlo Presutti, Rodolfo Negri

Published in Cancer Science by Wiley.

2019   Volume 110, Issue 4, p1232-1243

Abstract

JARID1B/KDM5B histone demethylase's mRNA is markedly overexpressed in breast cancer tissues and cell lines and the protein has been shown to have a prominent role in cancer cell proliferation and DNA repair. However, the mechanism of its post-transcriptional regulation in cancer cells remains elusive. We performed a computational analysis of transcriptomic data from a set of 103 breast cancer patients, which, along with JARID1B upregulation, showed a strong downregulation of 2 microRNAs (miRNAs), mir-381 and mir-486, potentially targeting its mRNA. We showed that both miRNAs can target JARID1B 3'UTR and reduce luciferase's activity in a complementarity-driven repression assay. Moreover, MCF7 breast cancer cells overexpressing JARID1B showed a strong protein reduction when transfected with mir-486. This protein's decrease is accompanied by accumulation of DNA damage, enhanced radiosensitivity and increase of BRCA1 mRNA, 3 features previously correlated with JARID1B silencing. These results enlighten an important role of a miRNA's circuit in regulating JARID1B's activity and suggest new perspectives for epigenetic therapies.
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Type  article-journal
Stage   published
Date   2019-03-18
Language   en ?
DOI  10.1111/cas.13925
PubMed  30588710
PMC  PMC6447846
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