Oncotarget

Research Papers:

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

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

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Oncotarget. 2015; 6:26457-26471. https://doi.org/10.18632/oncotarget.4762

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Abstract

Shaohua Xu1,*, Guang-Bo Fu2,*, Zhen Tao4, Jun OuYang5, Fanfei Kong1, Bing-Hua Jiang6,7, Xiaoping Wan1 and Ke Chen3

1 Department of Obstetrics and Gynecology, Shanghai First Matenity and Infant Hospital, Tongji University School of Medicine, Shanghai, China

2 Department of Urology and Pathology, Huai’an First People’s Hospital, Nanjing Medical University, Huai’an, China

3 Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

4 Department of Science and Technology, Radiation Oncology Department, Tianjin Medical University Cancer Hospital and Institute, Tianjin, China

5 Changzhou Maternal and Child Health Hospital Affiliated to Nanjing Medical University, Changzhou, China

6 State Key lab of Reproductive Medicine, Cancer Center, Nanjing Medical University, China

7 Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA, USA

* These authors have contributed equally to this work

Correspondence to:

Xiaoping Wan, email:

Ke Chen, email:

Keywords: miR-497, mTOR, p70S6K1, cisplatin resistance, ovarian cancer

Received: January 13, 2015 Accepted: June 25, 2015 Published: July 03, 2015

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.


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