title: The microRNA miR-33a suppresses IL-6-induced tumor progression by binding Twist in gallbladder cancer.
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.
authors: Department of General Surgery, Xinhua Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, 200092, China.|Department of Anesthesiology and Surgical Intensive Care Unit, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200092, China.
authors: Mingdi
authors: M
authors: Zhang
authors: Department of General Surgery, Xinhua Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, 200092, China.
authors: Wei
authors: W
authors: Gong
authors: Department of Orthopedic Surgery, Xinhua Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, 200092, China.
authors: Bin
authors: B
authors: Zuo
authors: Department of General Surgery, Xinhua Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, 200092, China.
authors: Bingfeng
authors: B
authors: Chu
authors: Department of General Surgery, Xinhua Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, 200092, China.
authors: Zhaohui
authors: Z
authors: Tang
authors: Department of General Surgery, Xinhua Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, 200092, China.
authors: Yong
authors: Y
authors: Zhang
authors: Department of General Surgery, Xinhua Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, 200092, China.
authors: Yong
authors: Y
authors: Yang
authors: Department of General Surgery, Xinhua Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, 200092, China.
authors: Di
authors: D
authors: Zhou
authors: Department of General Surgery, Xinhua Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, 200092, China.
authors: Mingzhe
authors: M
authors: Weng
authors: Department of General Surgery, Xinhua Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, 200092, China.
authors: Yiyu
authors: Y
authors: Qin
authors: Department of General Surgery, Xinhua Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, 200092, China.
authors: Mingzhe
authors: M
authors: Ma
authors: Schulich School of Medicine and Dentistry, Western Ontario University, London, ON N6A 3K6, Canada.
authors: Alex
authors: A
authors: Jiang
authors: Department of Oncology, Xinhua Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, 200092, China.
authors: Fei
authors: F
authors: Ma
authors: Department of General Surgery, Xinhua Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, 200092, China.
authors: Zhiwei
authors: Z
authors: Quan
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D001665:Binding Sites; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D005706:Gallbladder Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology*; D053208:Kaplan-Meier Estimate; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014162:Transfection; D051879:Twist-Related Protein 1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; C508600:IL6 protein, human; D015850:Interleukin-6; C550416:MIRN33a microRNA, human; D035683:MicroRNAs; D009687:Nuclear Proteins; C103173:TWIST1 protein, human; D051879:Twist-Related Protein 1
keywords: epithelial–mesenchymal transition; gallbladder cancer; interleukin-6; microRNAs; twist