LncRNA-HANR exacerbates malignant behaviors of cholangiocarcinoma cells through activating Notch pathway

Abstract

Objectives: Cholangiocarcinoma (CHOL) is a malignant tumor from extrahepatic bile duct with poor prognosis. The critical roles of long non-coding RNAs (lncRNAs) in cancers including CHOL have been unveiled in recent decades. The present study was aimed to investigate the role and mechanism of a certain lncRNA, namely, hepatocellular carcinoma (HCC) associated long non-coding RNA (HANR) in CHOL. Methods: Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was applied for detecting gene expression. Functional assays were done for assessing CHOL cell malignancy and mechanistic assays were conducted for analyzing correlation between HANR and Notch signal pathway, as well as the relation between HANR and Notch intracellular domain (NICD) in CHOL cells. Results: HANR was detected to be significantly overexpressed in CHOL cell lines. HANR silence inhibited cell proliferation, migration and stemness. Besides, HANR could positively regulate the Notch signaling pathway through modulating RBP-JK. HANR could bind to NICD and affect the transcriptional activity of RBP-JK. Furthermore, p-Notch1-NICD-r could wholly countervail the inhibitory effects of HANR silence on CHOL cell proliferation, migration and stemness. Conclusion: HANR could activate Notch pathway by regulating the RBP-JK transcriptional activity, thus contributing to exacerbated malignant behaviors of CHOL cells.

Keywords

• HANR
• Cholangiocarcinoma
• Notch pathway
• NICD