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

Abstract 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_00...

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Main Authors: Kangjun Zhang, Taishi Fang, Qijun Chen, Xu Yan, Xin Jin, Nan Ma
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-10618-6
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Summary:Abstract 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.
ISSN:2045-2322