Zhang Kangjun, Fang Taishi, Chen Qijun, Yan Xu, Jin Xin, Ma Nan
Department of Liver Surgery and Transplantation, Transplant Center, The Third People's Hospital of Shenzhen (The Second Affiliated Hospital of Southern University of Science and Technology), No. 29 Bulan Road, Longgang District, Shenzhen, 518000, Guangdong Province, China.
Sci Rep. 2025 Jul 8;15(1):24580. doi: 10.1038/s41598-025-10618-6.
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.
环状RNA（circRNAs）在肝细胞癌（HCC）进展中起关键作用。尽管预测circ_0008043在HCC组织中高表达，但其功能作用和分子机制仍知之甚少。在本研究中，我们研究了circ_0008043对HCC转移的影响及其对miR-661/PLEKHG4B轴的调控。功能试验表明，circ_0008043敲低可抑制HCC细胞活力、迁移和上皮-间质转化（EMT）。机制上，circ_0008043作为miR-661的海绵，miR-661直接靶向PLEKHG4B。挽救实验表明，抑制miR-661或过表达PLEKHG4B可抵消circ_0008043沉默或miR-661过表达的作用。此外，我们确定ESRP1是促进circ_0008043生物合成的关键调节因子。体内实验证实，circ_0008043敲低可显著抑制肺转移。总体而言，我们的研究结果表明，ESRP1来源的circ_0008043通过调节miR-661/PLEKHG4B轴促进HCC细胞迁移和EMT，从而促进肿瘤转移。本研究为HCC进展的分子机制提供了新的见解，并为HCC治疗提出了潜在的治疗靶点。
