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MiR-497 decreases cisplatin resistance in ovarian cancer cells by targeting mTOR/P70S6K1.

By Shaohua Xu, Guang-Bo Fu, Zhen Tao, Jun OuYang, Fanfei Kong, Bing-Hua Jiang, Xiaoping Wan and Ke Chen

Abstract

The mechanism of cisplatin resistance in ovarian cancer is not clearly understood. In the present investigation, we found that the expression levels of miR-497 were reduced in chemotherapy-resistant ovarian cancer cells and tumor tissues due to hypermethylation of miR-497 promoter. Low miR-497 expression levels were associated with chemo-resistant phonotype of ovarian cancer. By analyzing the expression levels of miR-497, mTOR and p70S6K1 in a clinical gene-expression array dataset, we found that mTOR and p70S6K1, two proteins correlated to chemotherapy-resistance in multiple types of human cancers, were inversely correlated with miR-497 levels in ovarian cancer tissues. By using an orthotopic ovarian tumor model and a Tet-On inducible miR-497 expression system, our results demonstrated that overexpression of miR-497 sensitizes the resistant ovarian tumor to cisplatin treatment. Therefore, we suggest that miR-497 might be used as a therapeutic supplement to increase ovarian cancer treatment response to cisplatin

Topics: Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University; Cisplatin resistance; miR-497; mTOR; Ovarian cancer; p70S6K1, Medical Cell Biology
Publisher: Jefferson Digital Commons
Year: 2015
OAI identifier: oai:jdc.jefferson.edu:pacbfp-1174

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