Hou Panzhang, Kang Yi, Luo Jianchao
a Radiotherapy department , Henan Provicial people's Hospital , Zhengzhou , Henan province , China.
b Infectious Diseases department , Henan Provicial people's Hospital , Zhengzhou , China.
Cancer Biol Ther. 2018;19(11):984-993. doi: 10.1080/15384047.2018.1456608. Epub 2018 May 14.
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.
Rab1a是RAS癌基因家族的成员之一，已有报道称其在肿瘤增殖和迁移中发挥重要作用。然而，Rab1a在肝内胆管癌（ICC）中的作用尚不清楚。在本研究中，我们发现Rab1a在ICC组织中的mRNA和蛋白质水平均呈过表达。Kaplan-Meier分析表明，Rab1a的高表达与ICC患者的不良预后相关。抑制Rab1a可通过抑制细胞周期进程和上皮-间质转化（EMT），在体外和体内降低细胞增殖率和迁移能力。进一步研究表明，Rab1a受miR-212-3p靶向调控。此外，在缺氧条件下，Rab1a的表达增加而miR-212-3p的表达降低。总之，这些发现扩展了我们对Rab1a在ICC进展中作用的理解，并且我们发现缺氧/miR-212-3p/Rab1a通路在ICC进展中起重要作用。这一新发现的通路应能促进ICC新型治疗生物标志物的开发。
