circTMEM181 upregulates ARHGAP29 to inhibit hepatocellular carcinoma migration and invasion by sponging miR-519a-5p

Hepatol Res. 2023 Apr;53(4):334-343. doi: 10.1111/hepr.13870. Epub 2022 Dec 30.

Abstract

Aim: Circular RNAs (circRNAs) are a novel class of noncoding RNAs and are conserved in various species. Although numerous circRNAs have been identified, their role in cancer remains unclear.

Methods: The expression of circTMEM181 in 90 paired human hepatocellular carcinoma (HCC) and adjacent nontumor tissues were detected using quantitative reverse transcription-polymerase chain reaction. Transwell assay was performed for functional analysis of HCC cell migration and invasion. Luciferase reporter assay was used to verify the combination of circTMEM181 and miR-519a-5p.

Results: In this study, we identified a novel circRNA, named circTMEM181, was downregulated in HCC tissues. Decreased expression of circTMEM181 was associated with shorter overall survival of patients with HCC. CircTMEM181 overexpression reduced HCC cell migration and invasion abilities, while circTMEM181 knockdown increased cell motility. Mechanically, circTMEM181 could directly bind to miR-519a-5p and subsequently upregulate ARHGAP29 protein expression.

Conclusion: These data provide the first evidence of clinical significance and function of circTMEM181, and suggest the circTMEM181/miR-519a-5p/ARHGAP29 axis in HCC development.

Keywords: ARHGAP29; HCC; circRNAs; circTMEM181; miR-519a-5p.