An increasing amount of evidence shows that circular RNAs (circRNAs) have critical effects on cancer progression and development; however, the biological function and potential molecular mechanism of circRNAs in hepatocellular carcinoma (HCC) are still unclear. CircRNA sequencing was used to identify differentially expressed circRNAs between HCC tissue and adjacent normal tissue. We found that circ_0001459 expression was significantly elevated in HCC tissue and cell lines. Furthermore, in vitro and in vivo functional experiments were carried out to detect the effects of circ_0001459 on HCC growth and metastasis. Knockdown of circ_0001459 significantly inhibited the proliferation, migration, and invasion of HCC cells, whereas upregulation of circ_0001459 had the opposite effect. Moreover, bioinformatics analysis, dual-luciferase reporter assay, RNA immunoprecipitation, and fluorescence in situ hybridization assays were used to predict and verify the interaction between circ_0001459, miR-6165, and the target gene IGF1R. Downregulation of circ_0001459 decreased IGF1R expression and inhibited epithelial-to-mesenchymal transition, which could be rescued by treatment with a miR-6165 inhibitor. Mechanistically, we revealed that circ_0001459 could sponge miR-6165 and induce the upregulation of its downstream target IGF1R, thus significantly promoting the progression of HCC. Therefore, circ_0001459 could be a new potential therapeutic target for HCC patients.
Keywords: EMT; HCC; IGF1R; circ_0001459; miR-6165.
© 2022 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals LLC on behalf of New York Academy of Sciences.