State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Hepatology. 2010 Nov;52(5):1731-40. doi: 10.1002/hep.23904.
MicroRNAs (miRNAs) are small, noncoding RNAs that can act as oncogenes or tumor suppressors in human cancer. Our previous study showed that miR-125b was a prognostic indicator for patients with hepatocellular carcinoma (HCC), but its functions and exact mechanisms in hepatic carcinogenesis are still unknown. Here we demonstrate that miR-125b suppressed HCC cell growth in vitro and in vivo. Moreover, miR-125b increased p21Cip1/Waf1 expression and arrested cell cycle at G₁ to S transition. In addition, miR-125b inhibited HCC cell migration and invasion. Further studies revealed that LIN28B was a downstream target of miR-125b in HCC cells as miR-125b bound directly to the 3' untranslated region of LIN28B, thus reducing both the messenger RNA and protein levels of LIN28B. Silencing of LIN28B recapitulated the effects of miR-125b overexpression, whereas enforced expression of LIN28B reversed the suppressive effects of miR-125b.
These findings indicate that miR-125b exerts tumor-suppressive effects in hepatic carcinogenesis through the suppression of oncogene LIN28B expression and suggest a therapeutic application of miR-125b in HCC.
MicroRNAs (miRNAs) 是小的非编码 RNA，可以在人类癌症中充当癌基因或肿瘤抑制因子。我们之前的研究表明，miR-125b 是肝细胞癌 (HCC) 患者的预后指标，但它在肝发生中的功能和确切机制尚不清楚。在这里，我们证明 miR-125b 抑制 HCC 细胞在体外和体内的生长。此外，miR-125b 增加了 p21Cip1/Waf1 的表达，并将细胞周期阻滞在 G₁ 到 S 期过渡。此外，miR-125b 抑制 HCC 细胞迁移和侵袭。进一步的研究表明，LIN28B 是 HCC 细胞中 miR-125b 的下游靶标，因为 miR-125b 直接结合到 LIN28B 的 3'非翻译区，从而降低 LIN28B 的信使 RNA 和蛋白水平。沉默 LIN28B 再现了 miR-125b 过表达的效果，而 LIN28B 的强制表达则逆转了 miR-125b 的抑制作用。
这些发现表明，miR-125b 通过抑制癌基因 LIN28B 的表达在肝发生中发挥肿瘤抑制作用，并提示 miR-125b 在 HCC 中的治疗应用。
