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: Mingdi Zhang, Wei Gong, Bin Zuo, Bingfeng Chu, Zhaohui Tang, Yong Zhang, Yong Yang, Di Zhou, Mingzhe Weng, Yiyu Qin, Mingzhe Ma, Alex Jiang, Fei Ma, Zhiwei Quan
• Journal: Oncotarget (Oncotarget) Vol. 7 Issue 48 Pg. 78640-78652 (Nov 29 2016) ISSN: 1949-2553 [Electronic] United States
• PMID: 27769047 (Publication Type: Journal Article)

Chemical References

• 3' Untranslated Regions
• IL6 protein, human
• Interleukin-6
• MIRN33a microRNA, human
• MicroRNAs
• Nuclear Proteins
• TWIST1 protein, human
• Twist-Related Protein 1

Topics

• 3' Untranslated Regions
• Animals
• Binding Sites
• Cell Line, Tumor
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Epithelial-Mesenchymal Transition (drug effects)
• Gallbladder Neoplasms (genetics, metabolism, mortality, pathology)
• Gene Expression Regulation, Neoplastic
• Humans
• Interleukin-6 (pharmacology)
• Kaplan-Meier Estimate
• Mice, Nude
• MicroRNAs (genetics, metabolism)
• Neoplasm Invasiveness
• Nuclear Proteins (genetics, metabolism)
• Signal Transduction (drug effects)
• Time Factors
• Transfection
• Twist-Related Protein 1 (genetics, metabolism)