期刊
CANCER LETTERS
卷 386, 期 -, 页码 168-178出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2016.11.017
关键词
Ovarian cancer; miR-136; Notch3 signaling; Chemoresistance; Cancer stem cells
类别
资金
- Korean Government [NRF-2015-R1A2A2A01005197, KHIDI-HI16C1559]
To identify microRNAs (miRNAs) regulating Notch3 expression in association with paclitaxel resistance, candidate miRNAs targeting Notch3 were predicted using TargetScan. We found that miR-136 directly targets Notch3, and miR-136 was significantly downregulated in OSC tissues relative to normal control tissues, and low expression of miR-136 correlated with poor overall in ovarian cancer patients. Artificial miR-136 overexpression significantly reduced cell viability, proliferation, Cancer stem cell (CSC) spheroid formation, and angiogenesis, and increased apoptosis in paclitaxel-resistant SKpac cells compared with the effects of paclitaxel alone. miR-136 overexpression downregulated cell survival- (survivin, DNA-PK, pS6, S6) and cell cycle- (Cyclin Dl, NF-kappa B) related proteins, and anti-apoptotic proteins (BCL2, and BCL-XL), and upregulated pro-apoptotic proteins (Bim, Bid, and Bax). Taken together, miR-136 targets the Notch3 oncogene and functions as a tumor suppressor. miR-136 overexpression resensitized paclitaxel-resistant ovarian cancer cells and reduced CSC activities, suggesting a promising new target for the treatment of chemoresistant ovarian cancers. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
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