Circular RNA Circ_0020236 Inhibits Hepatocellular Carcinoma Cell Proliferation and Migration Through Modulating the...

Hepatocellular carcinoma (HCC) is one of the most metastatic and aggressive malignancies. Circular RNAs (circRNAs) are associated with the pathogenesis and prognosis of HCC. This study aimed to explore the role of circ_0020236 in HCC progression. Expression levels of circ_0020236, miR-1825, and IKBKB were assessed in HCC clinical samples and cell lines using quantitative real-time PCR. Bioinformatics predictions combined with dual-luciferase reporter, RNA immunoprecipitation, and RNA pull-down assays validated molecular interactions. Functional assays, including CCK-8, colony formation, and Transwell migration, were employed to evaluate cell proliferation and migration. The results indicated that circ_0020236 and IKBKB were significantly downregulated, whereas miR-1825 was upregulated in HCC. Ectopic expression of circ_0020236 suppressed HCC cell proliferation, migration, and tumor growth in vivo. Mechanistically, circ_0020236 functioned as a molecular sponge for miR-1825, which directly targeted IKBKB. Rescue experiments showed that miR-1825 overexpression reversed the tumor-suppressive effects of circ_0020236, while IKBKB knockdown abrogated the inhibitory phenotype induced by miR-1825 silencing. Furthermore, the RNA-binding protein ESRP2 was identified as a positive regulator of circ_0020236 biogenesis. In conclusion, our findings reveal that the ESRP2/circ_0020236/miR-1825/IKBKB axis plays a critical role in inhibiting HCC progression, positioning circ_0020236 as a promising therapeutic target for HCC intervention.