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微小RNA-127通过调控癌基因FMNL3在人食管鳞状细胞癌中发挥肿瘤抑制作用。

MicroRNA-127 is a tumor suppressor in human esophageal squamous cell carcinoma through the regulation of oncogene FMNL3.

作者信息

Gao Xuhui, Wang Xuelian, Cai Kaican, Wang Wujun, Ju Qun, Yang Xiyao, Wang Haofei, Wu Hua

机构信息

Department of Cardiothoracic Surgery, Wuhan General Hospital of Guangzhou Command, Wuhan 430000, China; Department of Cardiothoracic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.

Department of anesthesiology, The Third Affiliated Hospital, Southern Medical University, Guangzhou 510000, China.

出版信息

Eur J Pharmacol. 2016 Nov 15;791:603-610. doi: 10.1016/j.ejphar.2016.09.025. Epub 2016 Sep 17.

Abstract

In this study, we investigated the expression patterns and functional roles of microRNA 127 (miR-127) and its target gene Formin-Like 3 (FMNL3) in human esophageal squamous cell carcinoma (ESCC). Quantitative RT-PCR (qRT-PCR) was used to compare miR-127 expression between ESCC cell lines and normal esophageal epithelium cell line, as well as paired ESCC tumors and adjacent normal esophageal tissues in 33 patients. We found miR-127 was aberrantly downregulated in both ESCC cell lines and human ESCC tumors. In ESCC cell lines TE-1 and ECA109 cells, lentiviral-induced miR-127 upregulation markedly inhibited cancer proliferation and migration in vitro, and tumorigenicity in vivo. Through dual-luciferase assay and qRT-PCR, FMNL3 was confirmed to be the downstream target gene of miR-127 in ESCC. Finally, FMNL3 was downregulated by siRNA in TE-1 and ECA109 cells. And we discovered that SiRNA-induced FMNL3 downregulation had tumor suppressive effect in ESCC, inhibiting cancer proliferation, migration in vitro, and tumorigenicity in vivo. These results suggest that miR-127 is downregulated and acting as tumor suppressor in ESCC. Inversely, FMNL3, the target gene of miR-127, is upregulated and acting as an oncogene in ESCC.

摘要

在本研究中,我们调查了微小RNA 127(miR - 127)及其靶基因formin样蛋白3(FMNL3)在人食管鳞状细胞癌(ESCC)中的表达模式和功能作用。采用定量逆转录聚合酶链反应(qRT - PCR)比较ESCC细胞系与正常食管上皮细胞系之间以及33例患者的配对ESCC肿瘤组织和相邻正常食管组织中miR - 127的表达。我们发现miR - 127在ESCC细胞系和人ESCC肿瘤中均异常下调。在ESCC细胞系TE - 1和ECA109细胞中,慢病毒介导的miR - 127上调显著抑制了体外癌细胞的增殖和迁移以及体内的致瘤性。通过双荧光素酶报告基因检测和qRT - PCR,证实FMNL3是ESCC中miR - 127的下游靶基因。最后,在TE - 1和ECA109细胞中用小干扰RNA(siRNA)下调FMNL3。并且我们发现siRNA介导的FMNL3下调在ESCC中具有肿瘤抑制作用,可抑制体外癌细胞的增殖和迁移以及体内的致瘤性。这些结果表明,miR - 127在ESCC中表达下调并发挥肿瘤抑制作用。相反,miR - 127的靶基因FMNL3在ESCC中表达上调并发挥癌基因作用。

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