Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
Cell Biol Int. 2023 Sep;47(9):1519-1534. doi: 10.1002/cbin.12049. Epub 2023 May 19.
Circular RNAs (circRNAs) may be involved in tumorigenesis. Recently, the role of circRNAs in hepatocellular carcinoma (HCC) has drawn wide attention. Herein, we aimed to explore the regulation and function of hsa_circ_0005239 in the malignant biological behavior and angiogenesis of HCC, as well as the link between hsa_circ_0005239 and programmed cell death ligand 1 (PD-L1) in HCC. Quantitative real-time polymerase chain reaction (qRT-PCR) assays revealed that hsa_circ_0005239 was upregulated in HCC tumor samples and cell lines. Furthermore, a series of in vitro and in vivo assays explored the effects of hsa_circ_0005239 on biological processes involved in the development of HCC. Knockdown of hsa_circ_0005239 significantly inhibited cell migration, cell invasion, and angiogenesis in HCC, while overexpression showed the opposite effect. In the in vivo assays, hsa_circ_0005239 downregulation suppressed the growth of xenograft tumors in nude mice, which supported that hsa_circ_0005239 is a tumor promoter in HCC. Mechanistically, hsa_circ_0005239 binds to miR-34a-5p and functions as a competing endogenous RNA to modulate the expression of PD-L1. Further experiments revealed that the hsa_circ_0005239/PD-L1 axis regulates the malignant phenotypes of HCC cells through the phosphoinositide-3 kinase/protein kinase B (PI3K/Akt) signaling pathway. These results revealed the role of hsa_circ_0005239 and the hsa_circ_0005239/miR-34a-5p/PD-L1 axis in HCC, providing a potential diagnostic biomarker and therapeutic target for HCC.
环状 RNA（circRNAs）可能参与肿瘤发生。最近，circRNAs 在肝细胞癌（HCC）中的作用引起了广泛关注。本文旨在探讨 hsa_circ_0005239 在 HCC 恶性生物学行为和血管生成中的调控和功能，以及 hsa_circ_0005239 与 HCC 中程序性细胞死亡配体 1（PD-L1）之间的联系。实时定量聚合酶链反应（qRT-PCR）检测结果显示，hsa_circ_0005239 在 HCC 肿瘤组织和细胞系中上调。进一步的体外和体内实验探索了 hsa_circ_0005239 对 HCC 发展过程中涉及的生物学过程的影响。下调 hsa_circ_0005239 显著抑制 HCC 细胞迁移、侵袭和血管生成，而过表达则表现出相反的效果。在体内实验中，下调 hsa_circ_0005239 抑制裸鼠异种移植瘤的生长，这支持 hsa_circ_0005239 是 HCC 中的肿瘤促进因子。机制上，hsa_circ_0005239 与 miR-34a-5p 结合并作为竞争性内源性 RNA 调节 PD-L1 的表达。进一步的实验表明，hsa_circ_0005239/PD-L1 轴通过磷酸肌醇 3 激酶/蛋白激酶 B（PI3K/Akt）信号通路调节 HCC 细胞的恶性表型。这些结果揭示了 hsa_circ_0005239 和 hsa_circ_0005239/miR-34a-5p/PD-L1 轴在 HCC 中的作用，为 HCC 提供了潜在的诊断生物标志物和治疗靶点。
