Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China; Key Laboratory of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
Key Laboratory of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China; Department of Ultrasound, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
Biochem Biophys Res Commun. 2020 Dec 17;533(4):845-852. doi: 10.1016/j.bbrc.2020.07.035. Epub 2020 Sep 30.
Hepatocellular Carcinoma (HCC) is the main histological subtype of liver malignancy with poor prognosis. A growing body of evidence showed that Circular RNAs (circRNAs) are related to HCC tumorigenesis and progression. In this study, we investigated the function and regulation of circ-0038718 in HCC. We found that circ-0038718 was frequently elevated in HCC specimens and cell lines. High expression levels of circ-0038718 were correlated with unfavorable prognosis in HCC patients. Furthermore, we demonstrated that knockdown of circ-0038718 attenuated HCC cell proliferation and metastatic abilities, while overexpression of circ-0038718 resulted the converse effect. Silencing circ-0038717 inhibited HCC xenograft tumor development in vivo. Mechanistically, circ-0038718 acted as the sponge of tumor-suppressive miR-139-3p to regulate HCC progression. Rescue experiments suggested the oncogenic activity of circ-0038718 was partially exerted via modulating miR-139-3p expression. Inhibition of miR-139-3p abrogated the regulatory effect of circ-0038718 in HCC cells. In summary, our results unveiled that circ-0038718 could serve as an crucial regulator of HCC progression and provide a potential therapeutic target for HCC treatment.
肝细胞癌 (HCC) 是肝脏恶性肿瘤的主要组织学亚型，预后不良。越来越多的证据表明，环状 RNA (circRNAs) 与 HCC 的发生和发展有关。在本研究中，我们研究了 circ-0038718 在 HCC 中的功能和调控作用。我们发现 circ-0038718 在 HCC 标本和细胞系中频繁上调。circ-0038718 的高表达水平与 HCC 患者的不良预后相关。此外，我们证明了 circ-0038718 的敲低可减弱 HCC 细胞的增殖和转移能力，而过表达 circ-0038718 则产生相反的效果。circ-0038718 的沉默抑制了 HCC 异种移植肿瘤在体内的发展。机制上，circ-0038718 作为肿瘤抑制 miR-139-3p 的海绵，调节 HCC 的进展。挽救实验表明，circ-0038718 的致癌活性部分通过调节 miR-139-3p 的表达来发挥作用。抑制 miR-139-3p 可消除 circ-0038718 在 HCC 细胞中的调节作用。总之，我们的研究结果表明，circ-0038718 可以作为 HCC 进展的重要调节因子，并为 HCC 的治疗提供了一个潜在的治疗靶点。
