College of Basic Medical Sciences, Youjiang Medical University for Nationalities, Baise, China.
Department of Hepatobiliary Surgery, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China.
J Immunol Res. 2021 Oct 20;2021:3759879. doi: 10.1155/2021/3759879. eCollection 2021.
Accumulating evidence indicates that circular RNAs (circRNAs) can interact with microRNAs to modulate gene expression in various cancers, including hepatocellular carcinoma (HCC). Although the significant role of circRNAs has been well documented in HCC, the complex mechanisms of circRNAs still need to be elucidated. Our current study is aimed at investigating the function of circ_0001588 in HCC, which was observed to significantly increase in HCC tissues and cells. We demonstrated that the knockdown of circ_0001588 resulted in repressed cell proliferation, migration, and invasion. studies using a nude mouse model showed that circ_0001588 downregulation reduced tumor size. Moreover, miR-874 was predicted as a target of circ_0001588. Using luciferase binding assays, we proved that circ_0001588 functions as a molecular ceRNA of miR-874 and that CDK4 acts as a downstream target of miR-874 in HCC. It was confirmed that overexpression of miR-874 decreased the proliferation, migration, and invasion triggered by the increase in circ_0001588. In summary, our results indicate that circ_0001588 acts as a ceRNA and promotes HCC progression by targeting the miR-874/CDK4 signaling pathway. Hence, we propose that circ_0001588 may be a promising target for HCC treatment.
越来越多的证据表明，环状 RNA（circRNAs）可以与 microRNAs 相互作用，调节包括肝细胞癌（HCC）在内的多种癌症中的基因表达。尽管 circRNAs 在 HCC 中的重要作用已得到充分证实，但 circRNAs 的复杂机制仍有待阐明。我们目前的研究旨在研究 circ_0001588 在 HCC 中的功能，该 circRNA 在 HCC 组织和细胞中显著增加。我们证明，circ_0001588 的敲低导致细胞增殖、迁移和侵袭受到抑制。使用裸鼠模型的研究表明，circ_0001588 的下调降低了肿瘤的大小。此外，miR-874 被预测为 circ_0001588 的靶标。通过荧光素酶结合测定，我们证明 circ_0001588 作为 miR-874 的分子 ceRNA 发挥作用，并且 CDK4 是 HCC 中 miR-874 的下游靶标。证实过表达 miR-874 可降低 circ_0001588 增加引发的增殖、迁移和侵袭。综上所述，我们的研究结果表明，circ_0001588 通过靶向 miR-874/CDK4 信号通路作为 ceRNA 促进 HCC 进展。因此，我们提出 circ_0001588 可能是 HCC 治疗的有前途的靶点。
