Ni Hengli, Dai Xiaoxiao, Leng Xueqin, Deng Min, Qin Yan, Ji Qinghua, Xu Chunfang, Li Jianming, Liu Yao
Department of Pathology, Medical College of Soochow University, Suzhou, China.
Department of Pathology, The Second Affiliated Hospital of Soochow University, Suzhou, China.
J Cell Biochem. 2018 Aug;119(8):6806-6813. doi: 10.1002/jcb.26874. Epub 2018 Apr 25.
MiRNA isoforms (isomiRs) were defined as an addition or deletion of one or more nucleotides at the 5' or 3' ends or both. Different isomiRs of the same miRNA can target different genes, which have extended the regulatory scale medicated by miRNA. In this study, we systematically analyzed miRNA isoforms in hepatocellular carcinoma (HCC) based on The Cancer Genome Atlas (TCGA) data and further explore their role by in silico and in vitro studies. We found that higher variety and quantity of miR-139-5p isoforms negatively correlated with the malignancy of HCC. And patients with higher variety and quantity of iso-miR-139-5p exhibited favorable survival, independent of tumor stage. Interestingly, miR-139-5p -1|-1 showed increased complementary effect of its target IGF1R than the archetype of miR-139-5p, and could further inhibit cellular movement more vigorously than its archetype. In conclusion, not only miR-139-5p itself, but its isoforms' variety and quantity confer suppressive role in HCC.
微小RNA亚型（isomiRs）被定义为在5'或3'末端或两端有一个或多个核苷酸的添加或缺失。同一微小RNA的不同亚型可以靶向不同的基因，这扩展了微小RNA介导的调控范围。在本研究中，我们基于癌症基因组图谱（TCGA）数据系统分析了肝细胞癌（HCC）中的微小RNA亚型，并通过计算机模拟和体外研究进一步探索了它们的作用。我们发现，miR-139-5p亚型的更高多样性和数量与HCC的恶性程度呈负相关。并且，具有更高多样性和数量的iso-miR-139-5p的患者表现出良好的生存率，与肿瘤分期无关。有趣的是，miR-139-5p -1|-1与其原型相比，对其靶标IGF1R的互补作用增强，并且比其原型更能有力地抑制细胞运动。总之，不仅miR-139-5p本身，而且其亚型的多样性和数量在HCC中都具有抑制作用。
