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微小RNA-338-3p的下调促进了肝细胞癌中的血管生成。

Down-regulation of microRNA-338-3p promoted angiogenesis in hepatocellular carcinoma.

作者信息

Zhang Tong, Liu Wei, Zeng Xian-Cheng, Jiang Nan, Fu Bin-Sheng, Guo Y, Yi Hui-Ming, Li Hua, Zhang Qi, Chen Wen-Jie, Chen Gui-Hua

机构信息

Department of Hepatic Surgery and Liver transplantation Center of the Third Affiliated Hospital, Organ Transplantation Institute of Sun Yat-sen University, Organ Transplantation Research Center of Guangdong Province, Guangzhou 510630, China.

Guangdong Provincial Key Laboratory of Liver Disease Research, Guangzhou, Guangdong 510630, China ; Key Laboratory of Clinical & Translational Research on Biotherapy for Liver Disease of Guangdong Higher Education Institutes, Sun Yat-sen University ; Cell-Gene Therapy Translational Medicine Research Center of the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510630, China.

出版信息

Biomed Pharmacother. 2016 Dec;84:583-591. doi: 10.1016/j.biopha.2016.09.056. Epub 2016 Sep 29.

Abstract

miRNAs are involved in substantial biological passways, including tumorigenesis, cancer development and progression. Angiogenesis plays a vital role in the progression of hepatocellular carcinoma (HCC), and VEGF is closely associated with the angiogenesis. However, the molecular mechanism of miRNAs in regulation tumorigenesis of HCC remains to be investigated. In the present research, we confirmed that miR-338-3p was suppressed both in HCC tissues and HCC cell lines. Then the tube formation, transwell and Chorioallantoic membrane (CAM) assay were carried out, such indicated that down-regulation of miR-338-3p can sharply increased, while up-regulation drastically suppressed angiogenesis of HCC cells in vitro. Moreover, MACC1 is predicted to be a target of miR-338-3p and we checked the prediction through luciferase assay. And then, our research showed that negative correlation existed between miR-338-3p and MACC1, β-catenin and VEGF that has been reported participated in cancer behavior in HCC cell lines. Subsequently, our assays illustrated that suppression miR-338-3p can up-regulate MACC1, β-catenin and VEGF expression of HCC cells. In conclusion, our research discovered that miR-338-3p can contribute to HCC angiogenesis by targeting MACC1, β-catenin and VEGF.

摘要

微小RNA(miRNAs)参与大量生物学途径,包括肿瘤发生、癌症发展和进展。血管生成在肝细胞癌(HCC)进展中起关键作用,而血管内皮生长因子(VEGF)与血管生成密切相关。然而,miRNAs在调控HCC肿瘤发生中的分子机制仍有待研究。在本研究中,我们证实miR-338-3p在HCC组织和HCC细胞系中均受到抑制。随后进行了管腔形成、Transwell和鸡胚绒毛尿囊膜(CAM)试验,结果表明miR-338-3p的下调可显著增加,而其上调则可在体外显著抑制HCC细胞的血管生成。此外,预测巨噬细胞迁移抑制因子1(MACC1)是miR-338-3p的一个靶标,我们通过荧光素酶试验验证了该预测。然后,我们的研究表明miR-338-3p与MACC1、β-连环蛋白和VEGF之间存在负相关,且已有报道称它们参与HCC细胞系中的癌症行为。随后,我们的试验表明抑制miR-338-3p可上调HCC细胞中MACC1、β-连环蛋白和VEGF的表达。总之,我们的研究发现miR-338-3p可通过靶向MACC1、β-连环蛋白和VEGF促进HCC血管生成。

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