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
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