American journal of cancer research · 2016
MicroRNA-133a-3p exerts inhibitory effects on gallbladder carcinoma via targeting RBPJ.
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Huang Yuan, Wu Yaoshi, Dong Jiahong, Han Dongdong, Yang Shiwei, Jiang Lin
Аннотация
Gallbladder carcinoma (GBC) is the most common biliary tract malignancy with high mortality. The median survival time is 6 months, and the 5-year survival rate less than 5% for GBC patients. Thus, it is imperative to investigate the molecular mechanisms underlying the pathogenesis of GBC. miR-133a may exert anti-tumor effects on a variety of cancers. However, the role of miR-133a in the pathogenesis of GBC remains unclear. In this study, quantitative real-time polymerase chain reaction (qRT-PCR) showed the miR-133a-3p expression markedly decreased in GBC as compared to adjacent normal tissues. Transient over-expression of miR-133a-3p inhibited the proliferation, migration and invasion abilities of GBC cells. Luciferase activity assay indicated that miR-133a-3p negatively regulated the expression of recombination signal-binding protein Jκ (RBPJ) directly, which is a key downstream transcription factor in the Notch signaling pathway. Moreover, PBPJ expression was up-regulated and negatively related to miR-133a-3p expression in GBC, and silencing of RBPJ achieved the effects as after miR-133a-3p over-expression. RBPJ over-expression could markedly reverse the inhibitory effects of miR-133a-3p on the proliferation, migration and invasion of GBC cells. Our findings indicate that miR-133a-3p acts as a tumor suppressor through directly targeting RBPJ in GBC.