LncRNA HEIH promotes cell proliferation, migration and invasion in cholangiocarcinoma by modulating miR-98-5p/HECTD4
Tao Wan, Hongguang Wang, Miaomiao Gou, Haiyan Si, Zhikuan Wang, Huan Yan, Tiee Liu, Shiyun Chen, Runjia Fan, Niansong Qian, Guanghai Dai
Abstract
To date, a large set of long non-coding RNAs (lncRNAs) have been identified in tumorigenesis and progression. The present study focused on functions and mechanisms of HEIH in cholangiocarcinoma (CHOL). We started this study by testing the expression of HEIH in CHOL tissues by qRT-PCR technology. Next, loss-of-function experiments demonstrated the oncogenic nature of HEIH in CHOL. We also used bioinformatics tools to select miRNAs and mRNAs for support of the ceRNA network. Mechanistic experiments including RIP assay, luciferase reporter assay were carried out for further confirmation of binding situation among ceRNA molecules. At last, rescue experiments proved the ceRNA axis in CHOL. According to the results, HEIH expression was up-regulated in CHOL tissues and cells. Functionally, knockdown of HEIH attenuated cell proliferation, migration and invasion. Mechanistically, bioinformatics analysis, RIP assay and luciferase assay verified the ceRNA network among HEIH, miR-98-5p and HECTD4. Rescue experiments further demonstrated the oncogenic role of HEIH and HECTD4. The final in vivo experiments suggested that knockdown of HEIH restrained tumor growth both in weight and volume. In conclusion, HEIH promoted CHOL tumorigenesis and progression by miR-98-5p/HECTD4 axis, which opens up a new insight for CHOL therapeutics.