Department of Anesthesiology, Luzhou People's Hospital, Southwest Medical University, Luzhou, 646000, Sichuan, PR China.
Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, 646000, Sichuan, PR China.
Mol Cancer. 2024 Aug 6;23(1):159. doi: 10.1186/s12943-024-02074-z.
Circular RNA (circRNA) is thought to mediate the occurrence and development of human cancer and usually acts as a tiny RNA (miRNA) sponge to regulate downstream gene expression. However, it is not clear whether and how circACVR2A (hsa_circ_0001073) is involved in the progression of HCC. The purpose of this study is to clarify the potential role and molecular mechanism of circACVR2A in regulating the progression of hepatocellular carcinoma cells (HCC). The abundance of related proteins in circACVR2A, microRNA (miR511-5p) and PI3K-Akt signaling pathway was determined by quantitative reverse transcriptase polymerase chain reaction (RT-PCR) or Western blotting. Cell viability, invasion and apoptosis were analyzed by CCK-8, Transwell analysis and Tunel staining, respectively. The interaction between circACVR2A and microRNA was evaluated by double luciferase reporter gene assay. The results showed that circACVR2A was highly expressed in hepatocellular carcinoma cell lines. Our in vivo and in vitro data showed that circACVR2A promoted the proliferation, migration and invasion of HCC. In terms of mechanism, we found that circACVR2A can directly interact with miR511-5p and act as a miRNA sponge to regulate the expression of related proteins in PI3K-Akt signaling pathway.In HCC, circACVR2A can mediate miR-511-5p/mRNA network to activate PI3K signal pathway. This shows that the molecular regulatory network with circACVR2A as the core is a new potential target for diagnosis and treatment of hepatocellular carcinoma.
环状 RNA（circRNA）被认为介导人类癌症的发生和发展，通常作为微小 RNA（miRNA）海绵来调节下游基因表达。然而，circACVR2A（hsa_circ_0001073）是否以及如何参与 HCC 的进展尚不清楚。本研究旨在阐明 circACVR2A 在调节肝细胞癌细胞（HCC）进展中的潜在作用和分子机制。通过定量逆转录聚合酶链反应（RT-PCR）或 Western blot 测定 circACVR2A、microRNA（miR511-5p）和 PI3K-Akt 信号通路相关蛋白的丰度。分别通过 CCK-8、Transwell 分析和 Tunel 染色分析细胞活力、侵袭和凋亡。通过双荧光素酶报告基因检测评估 circACVR2A 与 microRNA 之间的相互作用。结果表明，circACVR2A 在肝癌细胞系中高表达。我们的体内和体外数据表明，circACVR2A 促进 HCC 的增殖、迁移和侵袭。就机制而言，我们发现 circACVR2A 可以直接与 miR511-5p 相互作用，并作为 miRNA 海绵调节 PI3K-Akt 信号通路中的相关蛋白表达。在 HCC 中，circACVR2A 可以介导 miR-511-5p/mRNA 网络激活 PI3K 信号通路。这表明以 circACVR2A 为核心的分子调控网络是诊断和治疗肝细胞癌的新潜在靶点。
