MiR-500a-5p regulates oxidative stress response genes in breast cancer and predicts cancer survival

Davide Degli Esposti, Vasily N. Aushev, Eunjee Lee, Marie Pierre Cros, Jun Zhu, Zdenko Herceg, Jia Chen, Hector Hernandez-Vargas

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

MicroRNAs (miRNAs) are small regulatory non-coding RNAs with a diversity of cellular functions, and are frequently dysregulated in cancer. Using a novel computational method (ActMir) that we recently developed, the "activity" of miRNA hsa-miR-500a was implicated in estrogen receptor (ER) positive breast cancer; however its targets and functional impact remain poorly understood. Here, we performed an extensive gene expression analysis in ER+ breast cancer cell lines, to reveal the targets of miR-500a-5p after experimental modulation of its levels. We found that among mRNAs targeted by miR-500a-5p there was enrichment in oxidative stress response genes. Moreover, in vitro exposure to oxidative stress using H2O2 induces miR-500a-5p overexpression and downregulation of the oxidative stress targets TXNRD1 and NFE2L2. Finally, expression of several of the identified miR-500a-5p targets related to oxidative stress, including TXNRD1, was associated with ER+ breast cancer survival in multiple datasets. Overall, we identify miR-500a-5p as an oxidative stress response miRNA whose activity may define breast cancer progression and survival.

Original languageEnglish
Article number15966
JournalScientific Reports
Volume7
Issue number1
DOIs
StatePublished - 1 Dec 2017

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