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.
Keywords: Gallbladder carcinoma; miR-133a-3p; molecular mechanism; recombination signal-binding protein Jκ.