Journal Article

miR-520h is crucial for DAPK2 regulation and breast cancer progression

Jiang, S-S, Wang, M-Y, Hong, C-C, Chang, J-Y, Su, C-M, Wu, C-H, Chen, H-A, Su, J-L, Sung, S-Y, Su, Y-H, Chen, L-T, Chen, P-S, Chang, Y-W, Huang, M-T

2016

Overview

MicroRNAs (miRNAs) are small RNAs that suppress gene expression by their interaction with 3’untranslated region of specific target mRNAs. Although the dysregulation of miRNAs has been identified in human cancer, only a few of these miRNAs have been functionally documented in breast cancer. Thus, defining the important miRNA and functional target involved in chemoresistance is an urgent need for human breast cancer treatment. In this study, we, for the first time, identified a key role of miRNA 520h (miR-520h) in drug resistance. Through protecting cells from paclitaxel-induced apoptosis, expression of miR-520h promoted the drug resistance of human breast cancer cells. Bioinformatics prediction, compensatory mutation and functional validation further confirmed the essential role of miR-520h-suppressed Death-associated protein kinase 2 (DAPK2) expression, as restoring DAPK2 abolished miR-520h-promoted drug resistance, and knockdown of DAPK2 mitigated cell death caused by the depletion of miR-520h. Furthermore, we observed that higher level of miR-520h is associated with poor prognosis and lymph node metastasis in human breast cancer patients. These results show that miR-520h is not only an independent prognostic factor, but is also a potential functional target for future applications in cancer therapeutics.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 13/106 / 13/109 / 13/2 / 13/31 / 13/51 / 13/89 / 3' Untranslated regions / 38/89 / 631/67/1347 / 631/67/395 / 631/80/82/23 / Analysis / Apoptosis / Apoptosis - drug effects / Bioinformatics / Breast cancer / Breast Neoplasms - drug therapy / Breast Neoplasms - genetics / Breast Neoplasms - pathology / Care and treatment / Cell adhesion & migration / Cell Biology / Cell death / Cell Line, Tumor / Chemoresistance / Complications and side effects / Death-associated protein kinase / Death-Associated Protein Kinases - biosynthesis / Death-Associated Protein Kinases - genetics / Development and progression / Disease Progression / Drug resistance / Drug Resistance, Neoplasm - genetics / Female / Gene expression / Gene Expression Regulation, Neoplastic - drug effects / Human Genetics / Humans / Internal Medicine / Kinases / Lymph nodes / Medicine / Medicine & Public Health / Metastases / Metastasis / MicroRNAs / MicroRNAs - biosynthesis / MicroRNAs - genetics / miRNA / Oncology / original-article / Paclitaxel / Paclitaxel - administration & dosage / Ribonucleic acid / Risk factors / RNA / RNA, Messenger - biosynthesis