Shen Yuan, Liu Shanshan, Yuan Hanyu, Ying Xiaomin, Fu Hanjiang, Zheng Xiaofei
1 Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, China.
2 Beijing Institute of Basic Medical Sciences, Beijing, China.
Tumour Biol. 2017 May;39(5):1010428317705756. doi: 10.1177/1010428317705756.
Long non-coding RNAs have been revealed to play important roles in the progression of hepatocellular carcinoma. However, the detailed mechanisms underlying their activities are not fully understood. Using microarray technology, a number of long non-coding RNAs were previously identified to be aberrantly expressed in hepatocellular carcinoma. In this study, one of these long non-coding RNAs, designated lncRNA-PE (lncRNA promotes epithelial-mesenchymal transition), was further explored to study its expression profile and function. A cohort of human hepatocellular carcinoma tissue samples combined with benign controls and established human hepatocellular carcinoma cell lines were examined for the expression of lncRNA-PE. The biological functions of lncRNA-PE were examined by wound-healing and Transwell assays, which revealed that lncRNA-PE promotes cell invasion and migration. By detecting the level of epithelial-mesenchymal transition markers, lncRNA-PE was revealed to promote epithelial-mesenchymal transition in hepatocellular carcinoma cells. Further study suggested that lncRNA-PE downregulated miR-200a/b by repressing the primary transcript expression, enhanced ZEB1 expression, and promoted epithelial-mesenchymal transition of hepatocellular carcinoma cells. All these data imply that lncRNA-PE might play an important role in hepatocellular carcinoma development via the miR-200a/b-ZEB1 pathway.
长链非编码RNA已被揭示在肝细胞癌进展中发挥重要作用。然而,其作用的详细机制尚未完全阐明。利用微阵列技术,先前已鉴定出许多长链非编码RNA在肝细胞癌中异常表达。在本研究中,对其中一种名为lncRNA-PE(长链非编码RNA促进上皮-间质转化)的长链非编码RNA进行了进一步研究,以探讨其表达谱和功能。检测了一组人类肝细胞癌组织样本以及良性对照和已建立的人类肝癌细胞系中lncRNA-PE的表达。通过伤口愈合和Transwell实验检测lncRNA-PE的生物学功能,结果显示lncRNA-PE促进细胞侵袭和迁移。通过检测上皮-间质转化标志物的水平,发现lncRNA-PE促进肝癌细胞的上皮-间质转化。进一步研究表明,lncRNA-PE通过抑制初级转录本表达下调miR-200a/b,增强ZEB1表达,并促进肝癌细胞的上皮-间质转化。所有这些数据表明,lncRNA-PE可能通过miR-200a/b-ZEB1途径在肝癌发生发展中发挥重要作用。