Department of General Surgery, Shanghai First People's Hospital, Nanjing Medical University, Nanjing, China.
Department of General Surgery, Wuxi Third People's Hospital, Wuxi, China.
Front Biosci (Landmark Ed). 2018 Jan 1;23(2):388-396. doi: 10.2741/4596.
Available evidence suggests that autophagy may serve as a tumor suppressor in cases of chronic liver disease and liver cirrhosis and that autophagic deficiency may lead to hepatocellular carcinoma (HCC). Recent studies suggested that the development of several tumor types could be regulated by microRNA-181a. However, the role of miR-181a in the autophagy of HCC remains unclear. In this study, we aimed to investigate the role of miR-181a in the autophagy of HCC. We found that the mRNA expression of miR-181a is higher but the level of autophagy is lower in human HCC compared to normal liver tissue. A luciferase assay confirmed that Atg5 is the target gene of miR-181a. Moreover, the results showed that an miR-181a sponge increased apoptosis in HepG2 cells and reduced the growth of tumors in a HepG2 cell xenograft tumor model. In conclusion, these results suggest that miR-181a can inhibit autophagy in HCC by targeting Atg5, resulting in decreased apoptosis of HCC cells and increased tumor growth.
现有证据表明，自噬在慢性肝病和肝硬化的情况下可能作为肿瘤抑制因子发挥作用，而自噬缺陷可能导致肝细胞癌（HCC）。最近的研究表明，几种肿瘤类型的发展可以受到 microRNA-181a 的调控。然而，miR-181a 在 HCC 自噬中的作用尚不清楚。在本研究中，我们旨在研究 miR-181a 在 HCC 自噬中的作用。我们发现与正常肝组织相比，人 HCC 中 miR-181a 的 mRNA 表达更高，但自噬水平更低。荧光素酶报告基因实验证实 Atg5 是 miR-181a 的靶基因。此外，结果表明，miR-181a 海绵可增加 HepG2 细胞的凋亡，并减少 HepG2 细胞异种移植瘤模型中的肿瘤生长。总之，这些结果表明，miR-181a 可以通过靶向 Atg5 抑制 HCC 中的自噬，从而导致 HCC 细胞凋亡减少和肿瘤生长增加。
