The microRNA miR-33a suppresses IL-6-induced tumor progression by binding Twist in gallbladder cancer
Autor: | Ming-zhe Ma, Yong Yang, Bingfeng Chu, Yong Zhang, Wei Gong, Di Zhou, Ming-Di Zhang, Yiyu Qin, Alex Jiang, Bin Zuo, Zhaohui Tang, Mingzhe Weng, Fei Ma, Zhiwei Quan |
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Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
Oncology Pathology medicine.medical_specialty Epithelial-Mesenchymal Transition Time Factors medicine.medical_treatment Mice Nude Kaplan-Meier Estimate epithelial–mesenchymal transition Transfection Metastasis gallbladder cancer 03 medical and health sciences 0302 clinical medicine Cell Movement Cell Line Tumor Internal medicine microRNA medicine Animals Humans Neoplasm Invasiveness Epithelial–mesenchymal transition Gallbladder cancer Interleukin 6 3' Untranslated Regions Cell Proliferation Binding Sites biology Interleukin-6 business.industry Twist-Related Protein 1 Nuclear Proteins medicine.disease microRNAs Gene Expression Regulation Neoplastic 030104 developmental biology Cytokine Tumor progression 030220 oncology & carcinogenesis twist Cholecystitis biology.protein Gallbladder Neoplasms business Research Paper Signal Transduction |
Zdroj: | Oncotarget |
ISSN: | 1949-2553 |
Popis: | // Mingdi Zhang 1, 2 , Wei Gong 1 , Bin Zuo 3 , Bingfeng Chu 1 , Zhaohui Tang 1 , Yong Zhang 1 , Yong Yang 1 , Di Zhou 1 , Mingzhe Weng 1 , Yiyu Qin 1 , Mingzhe Ma 1 , Alex Jiang 4 , Fei Ma 5 , Zhiwei Quan 1 1 Department of General Surgery, Xinhua Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, 200092, China 2 Department of Anesthesiology and Surgical Intensive Care Unit, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200092, China 3 Department of Orthopedic Surgery, Xinhua Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, 200092, China 4 Schulich School of Medicine and Dentistry, Western Ontario University, London, ON N6A 3K6, Canada 5 Department of Oncology, Xinhua Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, 200092, China Correspondence to: Zhiwei Quan, email: zhiwquan@163.com Fei Ma, email: irismafei@126.com Keywords: gallbladder cancer, microRNAs, epithelial–mesenchymal transition, twist, interleukin-6 Received: January 23, 2016 Accepted: September 25, 2016 Published: October 15, 2016 ABSTRACT 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. |
Databáze: | OpenAIRE |
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