Circular RNA circDLG1 contributes to HCC progression by regulating the miR-141-3p/WTAP axis

Abstract

AbstractThis study aims to explore novel and reliable biomarkers for predicting hepatocellular carcinoma (HCC) prognosis. Circular RNAs (circRNAs) were determined by analysis of human circRNA arrays and quantitative reverse transcription polymerase reactions. To test for an interaction between circDLG1, we used luciferase reporter assays, RNA immunoprecipitation, and fluorescence in situ hybridization assays that were employed to test the interaction between circDLG1, miR-141-3p, and WTAP. q-RT-PCR and western blot were used to evaluate the target regulation of miR-141-3p and WTAP. shRNA-mediated knockdown of circDLG1, proliferation, migration, and invasion experiment of metastasis were used to evaluate the function of circDLG. CircDLG1 rather than lining DLG1 was upregulated in HCC tissues, from HCC patients as well as HCC cell lines compared to normal controls. circDLG1 high expression in HCC patients was correlated with shorter overall survival. Knockdown of circDLG1 and miR-141-3p mimic could inhibit the tumorigenesis of HCC cells in vivo and in vitro. Importantly, we demonstrated that circDLG1 could act as a sponge of miR-141-3p to regulate the expression of WTAP, and further suppress the tumorigenesis of HCC cells. Our study reveals that circDLG1 can serve as a novel potential circulating biomarker for the detection of HCC. circDLG1 participates in the progression of HCC cells by sponging miR-141-3p with WTAP, providing new insight into the treatment of HCC.