Hsa_circ_NOTCH3 regulates ZNF146 through sponge adsorption of miR-875-5p to promote tumorigenesis of hepatocellular carcinoma

Background: To explore the specific mechanism of circular RNA (circRNA) in the occurrence and development of hepatocellular carcinoma (HCC), and provide new ideas for its diagnosis and treatment. Methods: Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was for evaluating the expression of circ_NOTCH3 in liver cancer tissues and matched normal tissues and related cell lines. After overexpression or co-expression of circ_NOTCH3 or microRNA (miRNA) in cells, the changes in cell function were analyzed. Bioinformatics analysis and dual luciferase report analysis were utilized to predict and verify the binding site between circ_NOTCH3 and miRNA. Western blotting was applied to detect gene expression alterations. Additionally, in vivo tumor growth was also utilized to further assess the influence of knocking-down circ_NOTCH3 on the progression of HCC. Results: It was confirmed circ_NOTCH3 was highly expressed in HCC specimens and cells. The proliferation, migration, invasion, and oxaliplatin-resistance potential of HCC could be restrained by silencing circ_NOTCH3 or by ectopic expression of miR-875-5p in vitro. In terms of mechanism, circ_ NOTCH3 directly binds to miR-875-5p, regulating its activity by targeting the 3'-UTR of ZNF146. Overexpression of circ_NOTCH3 evidently overturned the diminishing influence of miR-875-5p mimics on HCC cells. Conclusions: As an oncogene, circ_NOTCH3 can trigger the proliferation, invasion, migration, and oxaliplatin resistance of HCC cells through the miR-875-5p/ZNF146 axis, and may be a promising target for the treatment of HCC.