Circ_0008043 promotes the metastasis of hepatocellular carcinoma by regulating the miR-661/PLEKHG4B axis.

Circular RNAs (circRNAs) play a critical role in hepatocellular carcinoma (HCC) progression. Although circ_0008043 is predicted to be highly expressed in HCC tissues, its functional role and molecular mechanisms remain poorly understood. In this study, we investigated the effects of circ_0008043 on HCC metastasis and its regulation of the miR-661/PLEKHG4B axis. Functional assays revealed that circ_0008043 knockdown suppressed HCC cell viability, migration, and epithelial-mesenchymal transition (EMT). Mechanistically, circ_0008043 acted as a sponge for miR-661, which directly targeted PLEKHG4B. Rescue experiments demonstrated that miR-661 inhibition or PLEKHG4B overexpression counteracted the effects of circ_0008043 silencing or miR-661 overexpression. Furthermore, we identified ESRP1 as a key regulator promoting circ_0008043 biogenesis. In vivo experiments confirmed that circ_0008043 knockdown significantly inhibited lung metastasis. Collectively, our findings reveal that ESRP1-derived circ_0008043 facilitates HCC cell migration and EMT by modulating the miR-661/PLEKHG4B axis, thereby promoting tumor metastasis. This study provides novel insights into the molecular mechanisms of HCC progression and suggests a potential therapeutic target for HCC treatment.