Yan Yan, Fan Qingxia, Wang Liping, Zhou Yue, Li Jianhua, Zhou Kun
Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Department of Medical Imaging, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Oncotarget. 2017 May 30;8(22):35750-35760. doi: 10.18632/oncotarget.16189.
Competing endogenous RNA (ceRNA) is a newly proposed mechanism that describes a crosstalk among lncRNAs, mRNAs and their shared miRNAs. In this study, the role of miR-338-3p (miR-338) in the progression of esophageal cancer and its involve in the ceRNA regulatory circuit lncRNA-Snhg1/CST3 were explored. MiR-338 displayed a 30% decreased expression in esophageal squamous cell carcinoma tissues compared with the adjacent. Then, proto-oncogene CST3 was predicted and validated as a target gene of miR-338. Gain-and-loss-function experiments indicated that miR-338 suppressed expression of CST3 protein (also Cystatin C, CysC), promoted expression of apoptotic proteins caspase-8/3, attenuated esophageal carcinoma cell growth and induced its apoptosis. In addition, lncRNA-Snhg1 was significantly upregulated in esophageal carcinoma tissues and promoted esophageal carcinoma cell growth. Furthermore, our results from bioinformatics, luciferase reporter gene and RNA pull-down assays indicated that Snhg1 could be directly bound by miR-338. Snhg1 acted as a non-degradable sponge to relieve the suppression on CST3 caused by miR-338. In conclusion, lncRNA-Snhg1 promoted cell proliferation by acting as a non-degradable sponge for the tumor suppressor miR-338 in esophageal cancer cells.
竞争性内源RNA(ceRNA)是一种新提出的机制,描述了长链非编码RNA(lncRNA)、信使核糖核酸(mRNA)及其共享的微小核糖核酸(miRNA)之间的相互作用。在本研究中,探讨了miR-338-3p(miR-338)在食管癌进展中的作用及其在ceRNA调控回路lncRNA-Snhg1/CST3中的参与情况。与癌旁组织相比,miR-338在食管鳞状细胞癌组织中的表达降低了30%。随后,原癌基因CST3被预测并验证为miR-338的靶基因。功能获得和缺失实验表明,miR-338抑制CST3蛋白(即胱抑素C,CysC)的表达,促进凋亡蛋白caspase-8/3的表达,减弱食管癌细胞的生长并诱导其凋亡。此外,lncRNA-Snhg1在食管癌组织中显著上调,并促进食管癌细胞的生长。此外,我们通过生物信息学、荧光素酶报告基因和RNA下拉实验得到的结果表明,Snhg1可被miR-338直接结合。Snhg1作为一种不可降解的海绵,可减轻miR-338对CST3的抑制作用。总之,lncRNA-Snhg1在食管癌细胞中作为肿瘤抑制性miR-338的不可降解海绵,促进细胞增殖。