MiR-31 regulates the cisplatin resistance by targeting Src in gallbladder cancer
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Maolan Li1,2,*, Wei Chen1,*, Hongchen Zhang1,2,*, Yong Zhang1, Fayong Ke1,2, Xiangsong Wu1,2, Yijian Zhang2, Mingzhe Weng1, Yingbin Liu1,2, Wei Gong1,2
1Department of General Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China
2The Institute of Biliary Disease Research, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China
*These authors have contributed equally to this work
Wei Gong, email: [email protected]
Keywords: gallbladder cancer, miR-31, DDP, src, drug resistance
Received: January 23, 2016 Accepted: September 25, 2016 Published: November 04, 2016
Background: Gallbladder cancer (GBC) is a malignant tumor highly resistant to chemotherapy. MicroRNAs (miRNAs) are found extensively involved in modulation of carcinogenesis and chemoresistance. This study aimed to investigate cisplatin (DDP)-susceptibility regulated by expression of the miRNAs and underlying pathways in GBC.
Results: The microRNA-31 (miR-31) was selected by microarray due to the biggest fold change between DDP-resistant and parental cells. Ectopic overexpression of miR-31 decreased cell proliferation, viability and invasion capacity, but promoted apoptosis in DDP-resistant cells and in xenograft tumor models. Cell apoptosis and DDP-chemosensitivity was remarkably increased by knockdown of Src proto-oncogene (Src) expression, which was subsequently reversed by rescue of Src expression in miR-31-expressing cells.
Methods: The microarray was used to select the candidate miRNA in two DDP-resistant GBC cell lines. The effect of regulated expression of the miRNA on cell migration, invasion, proliferation and apoptosis was examined by wound healing, transwell assays, CCK-8 assays, colony formation and flow cytometry assays, respectively. Xenograft tumor models were used to validate the function of the downstream target.
Conclusion: Our results demonstrated that miR-31reduced significantly in GBC cells rendering resistance to cisplatin, and upregulated expression of miR-31 augmented chemosensitivity, presenting a therapeutic potential to overcome drug resistance in GBC.
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