Department of Hepatobiliary Surgery, Shandong Provincial Third Hospital, Cheeloo College of Medicine, Shandong UniversityJinanP.R. China.
Oncol Res. 2020 Sep 1;28(4):399-408. doi: 10.3727/096504020X15864296270581. Epub 2020 Apr 9.
miRNAs play an important role in progression of hepatocellular carcinoma (HCC). In this work, we assessed the function of miR-202 in human HCC and identified BCL2 as its target. We found miR-202 expression was found significantly downregulated, while BCL2 expression was markedly upregulated in HCC tissues and cell lines (HepG2, Hep3B, and HCCLM3). Both miR-202 and BCL2 were closely correlated with major vascular invasion and advanced TNM stage as well as overall survival of HCC patients. Overexpression of miR-202 significantly inhibited cell proliferation, induced apoptosis and cell cycle arrest at the G/G phase, and prevented tumor formation in a xenograft nude mouse model. Further, miR-202 dramatically inhibited migration, invasion, and epithelialmesenchymal transition. miR-202 bound to the 3-untranslated region (3-UTR) of BCL2 mRNA and downregulated the expression level of BCL2 protein. Exogenous BCL2 overexpression weakened the inhibitory effects of miR-202, while inhibition of BCL2 enhanced the inhibitory effects of miR-202. In conclusion, miR-202 serves as a tumor suppressor in HCC progression by downregulating BCL2 expression, indicating miR-202 might be a potential target for HCC.
miRNAs 在肝细胞癌(HCC)的进展中发挥重要作用。在这项工作中,我们评估了 miR-202 在人 HCC 中的功能,并鉴定了 BCL2 是其靶标。我们发现 miR-202 的表达显著下调,而 BCL2 的表达在 HCC 组织和细胞系(HepG2、Hep3B 和 HCCLM3)中明显上调。miR-202 和 BCL2 均与 HCC 患者的主要血管侵犯、晚期 TNM 分期以及总生存率密切相关。miR-202 的过表达显著抑制细胞增殖,诱导细胞凋亡和细胞周期停滞在 G/G 期,并在异种移植裸鼠模型中阻止肿瘤形成。此外,miR-202 显著抑制迁移、侵袭和上皮-间充质转化。miR-202 结合 BCL2 mRNA 的 3-UTR 并下调 BCL2 蛋白的表达水平。外源性 BCL2 过表达减弱了 miR-202 的抑制作用,而 BCL2 的抑制增强了 miR-202 的抑制作用。总之,miR-202 通过下调 BCL2 的表达在 HCC 进展中起肿瘤抑制作用,表明 miR-202 可能是 HCC 的潜在治疗靶点。