Higher variety and quantity of microRNA-139-5p isoforms confer suppressive role in hepatocellular carcinoma
Higher variety and quantity of microRNA-139-5p isoforms confer suppressive role in hepatocellular carcinoma
复制标题
更高种类和数量的 microRNA-139-5p 同工型在肝细胞癌中具有抑制作用
DOI：
10.1002/jcb.26874
复制
发表时间：
2018-08-01
影响因子：
4
通讯作者：
Liu, Yao
中科院分区：
文献类型：
--
作者：
Ni, Hengli;Dai, Xiaoxiao;Liu, Yao
miRNA同种型（isomiR）被定义为在5或3端或两者处添加或缺失一个或多个核苷酸。同一miRNA的不同异构体可以靶向不同的基因，从而扩展了miRNA的调控范围。在这项研究中，我们系统地分析了miRNA异构体在肝细胞癌（HCC）的基础上癌症基因组图谱（TCGA）的数据，并进一步探讨其作用，通过在硅片和体外研究。我们发现miR-139- 5 p异构体的种类和数量与HCC的恶性程度呈负相关。具有较高的iso-miR-139- 5 p种类和数量的患者表现出有利的生存，与肿瘤分期无关。有趣的是，miR-139- 5 p-1|与miR-139- 5 p原型相比，miR-1 - 1显示了其靶IGF 1 R的增强的互补效应，并且可以比其原型更有力地进一步抑制细胞运动。总之，不仅miR-139- 5 p本身，而且其异构体的多样性和数量在HCC中赋予抑制作用。
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.