Hypoxia-mediated miR-212-3p downregulation enhances progression of intrahepatic cholangiocarcinoma through upregulation of Rab1a.

Rab1a, a member RAS oncogene family, has been reported playing important role in tumor proliferation and migration. However, the role of Rab1a in intrahepatic cholangiocarcinoma (ICC) is not clear. In this study, we found Rab1a was overexpressed in ICC tissues both in mRNA and protein level. Kaplan-meier analysis showed that high expression of Rab1a was associated with poor prognosis of ICC patients. Suppression of Rab1a led to lower proliferation rate and migration ability both in vitro and in vivo by inhibiting process of cell cycle and Epithelial-Mesenchymal Transition (EMT). Further study showed that Rab1a was targeting regulated by miR-212-3p.In addition, expression of Rab1a was increased while miR-212-3p was decreased under hypoxia condition. In conclusion, these findings extend our understanding of Rab1a in progression of ICC, and we found hypoxia/miR-212-3p/Rab1a pathway played important role for progression of ICC. This newly identified pathway should promote the development of novel therapeutic biomarker for ICC.