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microRNA-155 acts as an oncogene by targeting the tumor protein 53-induced nuclear protein 1 in esophageal squamous cell carcinoma

机译:microRNA-155通过靶向肿瘤蛋白53诱导的食管鳞状细胞癌中的核蛋白1来作为癌基因

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摘要

MicroRNA-155 (miR-155) is overexpressed in many human cancers; however, the function of miR-155 is largely unknown in esophageal squamous cell carcinoma (ESCC). In the present study, we found that miR-155 is dramatically increased in ESCC tissues compared with the paired adjacent normal tissues, which suggested that miR-155 acts as an oncogene in ESCC. We predicted that tumor protein p53-induced nuclear protein 1 (TP53INP1) is a candidate target gene of miR-155 given that miR-155 expression decreased mRNA and protein levels of TP53INP1 as determined by RT-PCR and Western blot analysis. In addition, miR-155 and TP53INP1 showed a negative relation in ESCC tissues. Dual luciferase-based reporter assay indicated direct regulation of TP53INP1 by miR-155. Furthermore, we demonstrated that RNA interference of TP53INP1 increased the proliferation and colonies formation of EC-1 cells. Up-regulation of TP53INP1 abrogated miR-155 induced growth in EC-1 cells and mutation of TP53INP1 in 3’-UTR restored the effects when co-transfected with miR-155. We also indicated that overexpression of miR-155 significantly promoted the proliferation of EC-1 cells in vitro and the development of tumors in nude mice. Taken together, our study reveals that miR-155 acts as an oncogene by targeting TP53INP1 in ESCC.
机译:MicroRNA-155(miR-155)在许多人类癌症中均过表达;然而,在食管鳞状细胞癌(ESCC)中,miR-155的功能很大程度上未知。在本研究中,我们发现与配对的相邻正常组织相比,ESCR组织中的miR-155显着增加,这表明miR-155在ESCC中起癌基因的作用。我们预测肿瘤蛋白p53诱导的核蛋白1(TP53INP1)是miR-155的候选靶基因,因为miR-155表达降低了TP53INP1的mRNA和蛋白水平,如RT-PCR和Western blot分析所确定。另外,miR-155和TP53INP1在ESCC组织中显示出负相关。基于双重荧光素酶的报告基因检测表明miR-155直接调节TP53INP1。此外,我们证明了TP53INP1的RNA干扰增加了EC-1细胞的增殖和集落形成。与miR-155共转染时,TP53INP1的上调消除了miR-155诱导的EC-1细胞生长,而3'-UTR中TP53INP1的突变恢复了该作用。我们还表明,miR-155的过表达在体外显着促进了EC-1细胞的增殖和裸鼠体内肿瘤的发展。综上所述,我们的研究揭示了miR-155通过靶向ESCC中的TP53INP1而作为癌基因。

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