Bao Hongbin, Li Xinguo, Li Hengli, Xing Hongli, Xu Binghui, Zhang Xianfeng, Liu Zhaoming
Department of Hepatobiliary Surgery, Harrison International Peace Hospital, Hengshui City, Hebei province, PR of China,
J Biosci. 2017 Mar;42(1):103-111. doi: 10.1007/s12038-016-9662-5.
MicroRNA 144 (miR-144), a small non-coding RNA, is frequently dysregulated in human several tumour progression, but its role and the underlying mechanisms in hepatocellular carcinoma (HCC) is poorly investigated. In the present study, the expression of miR-144 was firstly analysed in datasets derived from GSE21362 and TCGA, and then detected in HCC tissues and cell lines by quantitative RT-PCR (qRT-PCR) analysis. MiR-144 was shown to be significantly down-regulated in HCC tissues and cell lines. Subsequently, overexpression of miR-144 was transfected into HCC cell lines so as to investigate its biological function, including MTT, colony formation, and transwell assays. Gain of function assay revealed miR-144 remarkably inhibited cell proliferation, migration and invasion. In addition, bioinformatical analysis and luciferase reporter assay identified ZFX as a novel target of miR-144 in HCC cells, as confirmed by qRT-PCR and Western blot. Furthermore, ZFX was found to be significantly up-regulated using Oncomine database analysis. Loss of function assay further indicated knockdown of ZFX had similar effects of miR-144-mediated HCC cell proliferation and invasion. Therefore, miR-144 has been demonstrated to act as a tumour suppressor in HCC cell growth and motility by directly targeting ZFX, which implicates its potential applications in the development of HCC treatment.
微小RNA 144（miR - 144）是一种小型非编码RNA，在人类多种肿瘤进展过程中常常发生失调，但其在肝细胞癌（HCC）中的作用及潜在机制尚未得到充分研究。在本研究中，首先在源自GSE21362和TCGA的数据集中分析了miR - 144的表达，然后通过定量逆转录聚合酶链反应（qRT - PCR）分析在肝癌组织和细胞系中进行检测。结果显示，miR - 144在肝癌组织和细胞系中显著下调。随后，将miR - 144过表达转染到肝癌细胞系中，以研究其生物学功能，包括MTT、集落形成和Transwell实验。功能获得实验表明，miR - 144显著抑制细胞增殖、迁移和侵袭。此外，生物信息学分析和荧光素酶报告基因实验确定ZFX是肝癌细胞中miR - 144的一个新靶点，qRT - PCR和蛋白质免疫印迹法进一步证实了这一点。此外，通过Oncomine数据库分析发现ZFX显著上调。功能丧失实验进一步表明，敲低ZFX对肝癌细胞增殖和侵袭的影响与miR - 144介导的作用相似。因此，已证明miR - 144通过直接靶向ZFX在肝癌细胞生长和运动中发挥肿瘤抑制作用，这暗示了其在肝癌治疗开发中的潜在应用价值。
