The microRNA miR-33a suppresses IL-6-induced tumor progression by binding Twist in gallbladder cancer
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Mingdi Zhang1,2, Wei Gong1, Bin Zuo3, Bingfeng Chu1, Zhaohui Tang1, Yong Zhang1, Yong Yang1, Di Zhou1, Mingzhe Weng1, Yiyu Qin1, Mingzhe Ma1, Alex Jiang4, Fei Ma5, Zhiwei Quan1
1Department of General Surgery, Xinhua Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, 200092, China
2Department of Anesthesiology and Surgical Intensive Care Unit, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200092, China
3Department of Orthopedic Surgery, Xinhua Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, 200092, China
4Schulich School of Medicine and Dentistry, Western Ontario University, London, ON N6A 3K6, Canada
5Department of Oncology, Xinhua Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, 200092, China
Zhiwei Quan, email: firstname.lastname@example.org
Fei Ma, email: email@example.com
Keywords: gallbladder cancer, microRNAs, epithelial–mesenchymal transition, twist, interleukin-6
Received: January 23, 2016 Accepted: September 25, 2016 Published: October 15, 2016
Cytokine is a key molecular link between chronic inflammation and gallbladder cancer (GBC) progression. The potential mechanism of cytokine-associated modulation of microRNAs (miRNAs) expression in GBC progression is not fully understood. In this study, we investigated the biological effects and prognostic significance of interleukin-6 (IL-6) -induced miRNAs in the development of GBC. We identify that inflammatory cytokine, IL-6 promotes proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) of GBC both in vitro and in vivo. Among all the changed miRNAs in miRNA profiling, miR-33a expression was significantly decreased in IL-6 treated GBC cell lines, as well as in GBC tissues compared with case-matched normal tissues and cholecystitis tissues. In turn, miR-33a suppresses IL-6−induced tumor metastasis by directly binding Twist which was identified as an EMT marker. High expression of miR-33a suppressed xenograft tumor growth and dissemination in nude mice. The downregulation of miR-33a was closely associated with advanced clinical stage, lymph node metastasis, and poor clinical outcomes in patients with GBC. miR-33a acts as a tumor suppressor miRNA in GBC progression and may be considered for the development of potential therapeutics against GBC.
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