LncRNA HEIH modulates the proliferation, migration, and invasion of hepatocellular carcinoma cells by regulating the miR-193a-5p/CDK8 axis

Transl Cancer Res. 2024 Jan 31;13(1):423-436. doi: 10.21037/tcr-23-2228. Epub 2024 Jan 29.

Abstract

Background: Hepatocellular carcinoma (HCC), a malignant tumor with a high mortality rate, is a serious problem worldwide. This research sought to examine how long non-coding RNA (lncRNA) high expression in hepatocellular carcinoma (HEIH) affects the development and progression of HCC.

Methods: The expression of HEIH in HCC patients and HCC cell lines was measured by quantitative real-time polymerase chain reaction (qRT-PCR). Additionally, HEIH was knocked down, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide, wound-healing and transwell assays were conducted to evaluate the effects of HEIH on the proliferation, migration, and invasion of the HCC cells, respectively. A xenografted mice model was constructed to investigate the function of HEIH on HCC tumorigenesis in vivo. The interactions among HEIH, microRNA (miR)-193a-5p and cyclin-dependent kinase 8 (CDK8) were also investigated by dual luciferase reporter (DLR) gene and RNA immunoprecipitation (RIP) assays.

Results: HEIH was highly expressed in HCC tissues, and was correlated with advanced TNM stage and the absence of vascular invasion. The in vitro experiments showed that silencing HEIH restrained the viability, migration, and invasion of HCC cells, and hampered xenograft tumor growth in vivo. Additionally, HEIH was shown to bind directly to microRNA 193a-5p (miR-193a-5p) and facilitate the expression of the target gene CDK8 in the HCC cells. CDK8 overexpression and miR-193a-5p silencing attenuated the effects of si-HEIH-induced inhibition on the proliferation, migration, and invasion of HCC cells.

Conclusions: Silencing HEIH restrained the proliferation, migration, and invasion of HCC cells via the miR-193a-5p/CDK8 axis.

Keywords: Hepatocellular carcinoma (HCC); cyclin-dependent kinase 8 (CDK8); long non-coding RNA high expression in hepatocellular carcinoma (lncRNA HEIH); microRNA 193a-5p (miR-193a-5p).