Department of General Surgery, The Fourth Affiliated Hospital of China Medical University, Shenyang 110032, China.
Department of General Surgery, The Fourth Affiliated Hospital of China Medical University, Shenyang 110032, China.
Gene. 2019 May 20;697:94-102. doi: 10.1016/j.gene.2019.02.036. Epub 2019 Feb 20.
The pathogenesis and the underlying mechanisms of hepatocellular carcinoma (HCC) remain unclear. LncRNA plasmacytoma variant translocation 1 (PVT1) is an oncogene in a variety of cancers. The role of PVT1 in HCC progression is not completely understood. In the present study, we conducted a series of studies to explore the role of PVT1 on autophagy in HCC cells. Our study found PVT1 levels were markedly up-regulated in the corresponding HCC tissues. Importantly, we found that PVT1 could facilitate cell autophagy in HCC cells. Then, we confirmed that the effect of PVT1 promoting autophagy was dependent on regulating ATG3 expression. Further investigations revealed that PVT1 could upregulate autophagy-related gene 3 (ATG3) expression by acting as an endogenous sponge of miR-365, which was an inhibitor gene on ATG3 protein by targeting 3'UTR of ATG3 mRNA. Moreover, rescue assays indicated that the effect of PVT1 on autophagy of HCC cells were dependent on miR-365. In conclusion, our study demonstrated PVT1 might be a key regulator participating in autophagy in HCC cells. We proved that PVT1 could promote autophagy as ceRNA by targeting miR-365.
肝癌(HCC)的发病机制和潜在机制尚不清楚。浆细胞瘤变异易位 1(PVT1)是多种癌症中的癌基因。PVT1 在 HCC 进展中的作用尚不完全清楚。在本研究中,我们进行了一系列研究,以探讨 PVT1 在 HCC 细胞自噬中的作用。我们的研究发现,相应的 HCC 组织中 PVT1 水平明显上调。重要的是,我们发现 PVT1 可以促进 HCC 细胞的细胞自噬。然后,我们证实 PVT1 通过调节 ATG3 表达促进自噬的作用依赖于。进一步的研究表明,PVT1 可以通过充当 miR-365 的内源性海绵来上调自噬相关基因 3(ATG3)的表达,miR-365 是通过靶向 ATG3 mRNA 的 3'UTR 来抑制 ATG3 蛋白的抑制基因。此外,挽救实验表明,PVT1 对 HCC 细胞自噬的影响依赖于 miR-365。总之,我们的研究表明 PVT1 可能是参与 HCC 细胞自噬的关键调节因子。我们证明 PVT1 可以作为 ceRNA 通过靶向 miR-365 促进自噬。