MiR-199a-3p enhances cisplatin sensitivity of cholangiocarcinoma cells by inhibiting mTOR signaling pathway and expression of MDR1
| Autor: | Wei Chen, Liang Tao, Qiang Li, Jianghui Ma, Xuefeng Xia, Linjun Mo, Jie Ji |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Apoptosis MDR1 Cisplatin sensitivity Cholangiocarcinoma 03 medical and health sciences 0302 clinical medicine Cell Movement Cell Line Tumor medicine Humans ATP Binding Cassette Transporter Subfamily B Member 1 neoplasms PI3K/AKT/mTOR pathway Cell Proliferation Cisplatin business.industry TOR Serine-Threonine Kinases MTOR signaling pathway Gene Expression Regulation Neoplastic MicroRNAs chemosensitivity 030104 developmental biology Bile Duct Neoplasms Oncology Drug Resistance Neoplasm Cell culture 030220 oncology & carcinogenesis Immunology mTOR Cancer research Phosphorylation RNA Interference Mir 199a 3p business Signal Transduction Research Paper MiR-199a-3p medicine.drug |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.16834 |
| Popis: | // Qiang Li 1, * , Xuefeng Xia 1, * , Jie Ji 2 , Jianghui Ma 1 , Liang Tao 1 , Linjun Mo 3 , Wei Chen 4 1 Department of General Surgery, The Afflicted Drum Tower Hospital of Nanjing University Medical School, Nanjing, China 2 Nangjing Medical University, Nangjing, China 3 School of Surgery, The University of Western Australia, and Western Australia Liver and Kidney Surgical Transplant Service, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia 4 Institute of Molecular Engineering, University of Chicago, Chicago, Illinois, USA * These authors contributed equally to this work and share the first authorship Correspondence to: Qiang Li, email: liqiang0912@126.com Wei Chen, email: viogro@163.com Keywords: MiR-199a-3p, cholangiocarcinoma, mTOR, MDR1, chemosensitivity Received: December 14, 2016 Accepted: March 26, 2017 Published: April 04, 2017 ABSTRACT Several studies have reported reduced miRNA-199a-3p (miR-199a-3p) in different human malignancies, however, little is known about miR-199a-3p in cholangiocarcinoma cells. In this study, we demonstrate the essential role and mechanism of miR-199a-3p in regulating cisplatin sensitivity in cholangiocarcinoma cell lines. Using a CCK-8 cell counting assay we found that expression of miR-199a-3p was positively correlated with cisplatin sensitivity in cholangiocarcinoma cell lines. MiR-199a-3p overexpression could decrease the proliferation rate and increase apoptosis of cholangiocarcinoma cells in the presence of cisplatin, while miR-199a-3p inhibition had the opposite effect. Further study demonstrated that mTOR was the target gene of miR-199a-3p, and that miR-199a-3p mimics could inhibit expression of mTOR, which consequently reduced the phosphorylation of its downstream proteins 4EBP1 and p70s6k. Rescue experiments proved that miR-199a-3p could increase the cisplatin sensitivity of cholangiocarcinoma cell lines by regulating mTOR expression. Moreover, we also found that miR-199a-3p overexpression could reduce cisplatin induced MDR1 expression by decreasing the synthesis and increasing the degradation of MDR1, thus enhancing the effectiveness of cisplatin in cholangiocarcinoma. In conclusion, miR-199a-3p could increase cisplatin sensitivity of cholangiocarcinoma cell lines by inhibiting the activity of the mTOR signaling pathway and decreasing the expression of MDR1. |
| Databáze: | OpenAIRE |
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