Downregulation of circular RNA circPVT1 restricts cell growth of hepatocellular carcinoma through downregulation of Sirtuin 7 via microRNA-3666
Downregulation of circular RNA circPVT1 restricts cell growth of hepatocellular carcinoma through downregulation of Sirtuin 7 via microRNA-3666
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DOI：
10.1111/1440-1681.13273
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发表时间：
2020-02-27
影响因子：
2.9
通讯作者：
Wang, Yan
中科院分区：
文献类型：
--
作者：
Li, Yong;Shi, Haitao;Wang, Yan
环状RNA（circRNA）最近被认为是癌症发生和进展的关键调节因子，通常通过充当microRNA（miRNA）的竞争性内源RNA来调节基因表达。肝细胞癌（HCC）中circRNA的失调引起了广泛关注，但circRNA在HCC中的确切作用仍然很大程度上未知。在本研究中，我们旨在研究环状 RNA PVT1 (circPVT1)（一种新发现的癌症相关 circRNA）在 HCC 中的潜在作用。在此，我们发现 circPVT1 表达在 HCC 组织和细胞系中显着上调。 circPVT1 的敲低显着减少了 HCC 细胞的生长和集落形成，并增加了细胞凋亡。我们的结果进一步确定 circPVT1 作为 miR-3666 的海绵。 circPVT1 的敲低显着增加了 HCC 细胞中 miR-3666 的表达。此外，miR-3666的表达在HCC组织中显着下调，并且与circPVT1表达呈负相关。此外，miR-3666的过表达通过靶向Sirtuin 7 (SIRT7)抑制HCC细胞的生长。值得注意的是，miR-3666 抑制或 SIRT7 过表达部分逆转了 circPVT1 敲低介导的对 HCC 细胞生长的抑制作用。总体而言，这些结果表明，circPVT1 的下调通过上调 miR-3666 抑制 SIRT7 来抑制 HCC 细胞生长，表明 circPVT1 作为 HCC 的潜在治疗靶点。我们的研究强调了 circPVT1/miR-3666/SIRT7 在调节 HCC 细胞生长中的参与。
Circular RNAs (circRNAs) have been identified recently as pivotal regulators in the development and progression of cancers, generally by acting as competing endogenous RNAs of microRNAs (miRNAs) to regulate gene expression. The dysregulation of circRNAs in hepatocellular carcinoma (HCC) has attracted much attention, but the precise role of circRNAs in HCC remains largely unknown. In this study, we aimed to investigate the potential role of circular RNA PVT1 (circPVT1), a newly identified cancer-related circRNA, in HCC. Herein, we found that circPVT1 expression was significantly upregulated in HCC tissues and cell lines. Knockdown of circPVT1 significantly reduced the growth and colony formation, and increased cell apoptosis, of HCC cells. Our results further identified circPVT1 as a sponge for miR-3666. Knockdown of circPVT1 significantly increased miR-3666 expression in HCC cells. Moreover, miR-3666 expression was significantly downregulated in HCC tissues and was inversely correlated with circPVT1 expression. In addition, the overexpression of miR-3666 inhibited the growth of HCC cells by targeting Sirtuin 7 (SIRT7). Notably, miR-3666 inhibition or SIRT7 overexpression partially reversed the circPVT1 knockdown-mediated inhibitory effect on HCC cell growth. Overall, these results demonstrate that downregulation of circPVT1 represses HCC cell growth by upregulating miR-3666 to inhibit SIRT7, suggesting circPVT1 as a potential therapeutic target for HCC. Our study highlights the involvement of circPVT1/miR-3666/SIRT7 in regulating HCC cell growth.