Department of Medical Imaging, Affiliated Hospital of Nantong University, Jiangsu, 226001, China.
Department of Pharmacy, The People's Hospital of Hai tm)an County, Jiangsu, 226600, China.
Biomed Pharmacother. 2017 Jun;90:744-751. doi: 10.1016/j.biopha.2017.04.029. Epub 2017 Apr 15.
Aberrant expression of miRNAs has been documented to play critical roles in the development and progression of hepatocellular carcinoma (HCC). However, the expression pattern, functional roles and regulatory mechanism of miR-493-5p in HCC have not been addressed. Herein, we found that miR-493-5p was significantly downregulated in HCC tissues and was tightly associated with tumor size, tumor differentiation grade and TNM stage of HCC patients. Overexpression of miR-493-5p inhibited HCC cell proliferation, arrested cell cycle in G0/G1 phase and induced cell apoptosis. Bioinformatical analysis and luciferase reporter assay further proved that Golgiprotein73 (GP73), an oncogene which was generally overexpressed in HCC, acted as a novel target of miR-493-5p. MiR-493-5p could inhibit GP73 both mRNA and protein expression. Moreover, overexpression of GP73 could reverse the inhibitory effects of miR-493-5p mediated HCC cell proliferation. In addition, upregulated GP73 in HCC tissues was inversely correlated with the miR-493-5p expression levels in the HCC tissues. Collectively, our present study demonstrates that miR-493-5p is downregulated in HCC and it can suppress the proliferation of HCC cells, partly at least, via directly targeting GP73. Besides, this study provides a novel insight into the mechanism of hepatocarcinogenesis and a promising blueprint for miR-493-5p-GP73 axis-oriented treatment of HCC.
miR-493-5p 在肝癌中的表达模式、功能作用及其调控机制尚不清楚。本研究发现 miR-493-5p 在肝癌组织中显著下调,并与肝癌患者的肿瘤大小、肿瘤分化程度和 TNM 分期密切相关。过表达 miR-493-5p 抑制 HCC 细胞增殖,将细胞周期阻滞在 G0/G1 期,并诱导细胞凋亡。生物信息学分析和荧光素酶报告基因实验进一步证实,高尔基糖蛋白 73(GP73)作为一种在 HCC 中普遍过表达的癌基因,是 miR-493-5p 的一个新的靶基因。miR-493-5p 可以抑制 GP73 的 mRNA 和蛋白表达。此外,过表达 GP73 可以逆转 miR-493-5p 介导的 HCC 细胞增殖的抑制作用。另外,上调的 GP73 在肝癌组织中与肝癌组织中 miR-493-5p 的表达水平呈负相关。总之,本研究表明 miR-493-5p 在肝癌中下调,它可以通过直接靶向 GP73 抑制 HCC 细胞的增殖。此外,本研究为肝癌发生的机制提供了新的见解,并为 miR-493-5p-GP73 轴靶向治疗 HCC 提供了有前途的蓝图。