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

Authors

Shaohua Xu, Department of Obstetrics and Gynecology, Shanghai First Matenity and Infant Hospital, Tongji University School of MedicineFollow
Guang-Bo Fu, Department of Urology and Pathology, Huai'an First People's Hospital, Nanjing Medical University
Zhen Tao, Department of Science and Technology, Radiation Oncology Department, Tianjin Medical University Cancer Hospital and Institute
Jun OuYang, Changzhou Maternal and Child Health Hospital Affiliated to Nanjing Medical University
Fanfei Kong, Department of Obstetrics and Gynecology, Shanghai First Matenity and Infant Hospital, Tongji University School of Medicine
Bing-Hua Jiang, Lab of Reproductive Medicine, Department of Pathology, Cancer Center, Nanjing Medical University, Nanjing, Jiangsu, China; Department of Pathology, Anatomy and Cell Biology, and Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PennsylvaniaFollow
Xiaoping Wan, Department of Obstetrics and Gynecology, Shanghai First Matenity and Infant Hospital, Tongji University School of Medicine
Ke Chen, Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyFollow

Document Type

Article

Publication Date

9-22-2015

Comments

This article has been peer reviewed. It was published in: Oncotarget.

Volume 6, Issue 28, 2015, Pages 26457-26471.

The published version is available at DOI: 10.18632/oncotarget.4762

Copyright © 2015 The Authors

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.

Recommended Citation

Xu, Shaohua; Fu, Guang-Bo; Tao, Zhen; OuYang, Jun; Kong, Fanfei; Jiang, Bing-Hua; Wan, Xiaoping; and Chen, Ke, "MiR-497 decreases cisplatin resistance in ovarian cancer cells by targeting mTOR/P70S6K1." (2015). Department of Pathology, Anatomy, and Cell Biology Faculty Papers. Paper 173.
https://jdc.jefferson.edu/pacbfp/173

PubMed ID

26238185