Gao Xuhui, Wang Xuelian, Cai Kaican, Wang Wujun, Ju Qun, Yang Xiyao, Wang Haofei, Wu Hua
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.
Eur J Pharmacol. 2016 Nov 15;791:603-610. doi: 10.1016/j.ejphar.2016.09.025. Epub 2016 Sep 17.
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.
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。
