Research Papers:
Upregulation of microRNA-524-5p enhances the cisplatin sensitivity of gastric cancer cells by modulating proliferation and metastasis via targeting SOX9
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Abstract
Jing Wang1,*, Xiaofeng Xue2,*, Han Hong3,*, Mingde Qin4,*, Jin Zhou2, Qing Sun4, Hansi Liang4, Ling Gao2
1Department of General Surgery, The Second Hospital Affiliated to Jiaxing University, Jiaxing, 314000, Zhejiang Province, P.R. China
2Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, 215006, Jiangsu Province, P.R. China
3Department of Hepato-Pancreato-Biliary Surgery, Suzhou Municipal Hospital, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, 215006, Jiangsu Province, P.R. China
4The Stem Cell and Biomedical Material Key Laboratory of Jiangsu Province (The State Key Laboratory Incubation Base), Soochow University, Suzhou, 215006, Jiangsu Province, P.R. China
*These authors contributed equally to this work
Correspondence to:
Ling Gao, email: [email protected]
Keywords: gastric cancer, microRNA, MiR-524-5p, SOX9, chemoresistance
Received: July 14, 2016 Accepted: November 14, 2016 Published: November 21, 2016
ABSTRACT
Cisplatin-based chemotherapy is the most commonly used treatment regimen for gastric cancer (GC), however, the resistance to cisplatin represents the key limitation for the therapeutic efficacy. Aberrant expression of MiR-524-5p appears to be involves in tumorigenesis and chemoresistance. However, the mechanism by which miR-524-5p mediates effects of cisplatin treatment in GC remains poorly understood. Expressions of MiR-524-5p was detected in GC tissues and cell lines by qRT-PCR. Cell proliferation was observed by MTT assay; Cell migration was detected by transwell migration and invasion assay. The targeting protein of miR-524-5p was identified by luciferase reporter assay and western blot. We found that downregulation of miR-524-5p in GC tissues and cell lines. SC-M1 and AZ521 cells resistant to cisplatin expressed low levels of miR-524-5p in comparison to the sensitive parental cells. Overexpression of miR-524-5p expression in SC-M1 and AZ521 cells inhibited cell proliferation, migration, and invasion, and conferred sensitivity to cisplatin-resistant GC cells. Subsequently, we identified SOX9 as a functional target protein of miR-524-5p and found that SOX9 overexpression could counteracts the chemosensitizing effects of miR-524-5p. These results provide novel insight into the regulation of GC tumorigenesis and progression by miRNAs. Restoration of miR-524-5p may have therapeutic potential against GC.
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