COTE1 Facilitates Intrahepatic Cholangiocarcinoma Progression via Beclin1-Dependent Autophagy Inhibition.

Abstract

COTE1 was recently described as an oncogene in hepatocellular carcinoma and gastric cancer. However, the roles of COTE1 in intrahepatic cholangiocarcinoma (ICC) are little known. Our study is aimed at clarifying novel functions of COTE1 in ICC progression, including proliferation, invasion, and autophagy. By using quantitative real-time PCR, immunohistochemistry staining, and western blotting, we found that COTE1 expression was frequently upregulated in ICC tissues, compared to paracarcinoma tissues. High COTE1 expression was significantly correlated with aggressive clinical features and predicted poor prognosis of ICC patients. Functional experiments revealed that ectopic COTE1 expression promoted ICC cell proliferation, colony formation, cellular invasion, migration, and in vivo tumorigenicity; in contrast, COTE1 knockdown resulted in the opposite effects. At molecular mechanism in vitro and vivo, our study revealed that COTE1 overexpression suppressed autophagy via Beclin1 transcription inhibition; conversely, COTE1 silencing facilitated autophagy through promoting Beclin1 expression. Furthermore, the suppression of COTE1 knockdown on cellular growth and invasion was rescued/aggravated by Beclin1 inhibition/accumulation. Our data, for the first time, illustrate that COTE1 is an oncogene in ICC pathogenesis, and the ectopic COTE1 expression promotes ICC proliferation and invasion via Beclin1-dependent autophagy inhibition.