Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
Cancer Sci. 2019 Mar;110(3):973-984. doi: 10.1111/cas.13950. Epub 2019 Feb 23.
Despite the rapidly identified numbers of lncRNA in humans, exploration of the molecular mechanisms of lncRNA is lagging, because the molecular mechanisms of lncRNA can be various and complex in different conditions. In this study, we found a new molecular mechanism for a versatile molecule, MIR22HG. MIR22HG is an lncRNA that contributes to the initiation and progression of many human cancers, including hepatocellular carcinoma (HCC). We report that MIR22HG was downregulated in 120 HCC samples compared with adjacent nontumor liver tissues. More interestingly, decreased expression of MIR22HG in HCC could predict poor prognosis of HCC patients. Knockdown of MIR22HG promoted the growth, migration and invasion of HCC cells. In exploring the molecular mechanism of MIR22HG, we found that MIR22HG functioned as a tumor suppressor in hepatocellular carcinomas, in part through serving as a competing endogenous RNA to modulate the miRNA-10a-5p level. Moreover, NCOR2 was verified to act as the downstream target gene of MIR22HG/miR-10a-5p. In addition, the MIR22HG/miRNA-10a-5p/NCOR2 axis inhibited the activation of the Wnt/β-catenin pathway. Together, our results demonstrated that MIR22HG inhibited HCC progression in part through the miR-10a-5p/NCOR2 signaling axis and might act as a new prognostic biomarker for HCC patients.
尽管人类中快速鉴定出了大量的 lncRNA,但 lncRNA 的分子机制研究仍相对滞后,因为在不同条件下,lncRNA 的分子机制可能多种多样且复杂。在本研究中,我们发现了一种多功能分子 MIR22HG 的新分子机制。MIR22HG 是一种 lncRNA,它有助于许多人类癌症的发生和进展,包括肝细胞癌(HCC)。我们报告称,与相邻的非肿瘤肝组织相比,在 120 个 HCC 样本中 MIR22HG 的表达下调。更有趣的是,HCC 中 MIR22HG 的表达降低可以预测 HCC 患者的预后不良。敲低 MIR22HG 促进了 HCC 细胞的生长、迁移和侵袭。在探索 MIR22HG 的分子机制时,我们发现 MIR22HG 在肝细胞癌中作为肿瘤抑制因子发挥作用,部分是通过作为竞争性内源性 RNA 来调节 miRNA-10a-5p 的水平。此外,验证了 NCOR2 是 MIR22HG/miR-10a-5p 的下游靶基因。此外,MIR22HG/miRNA-10a-5p/NCOR2 轴抑制了 Wnt/β-catenin 通路的激活。总之,我们的研究结果表明,MIR22HG 通过 miR-10a-5p/NCOR2 信号轴抑制 HCC 进展,可能成为 HCC 患者的新预后生物标志物。