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微小RNA-153通过靶向卵巢癌细胞中的SET7和ZEB2发挥肿瘤抑制作用。

MicroRNA-153 functions as a tumor suppressor by targeting SET7 and ZEB2 in ovarian cancer cells.

作者信息

Zhou Jun, Xie Ming, Shi Ying, Luo Baihua, Gong Guanghui, Li Juanni, Wang Junpu, Zhao Wenjian, Zi Yuan, Wu Xiaoying, Wen Jifang

机构信息

Department of Pathology, School of Basic Medical Science, Central South University, Changsha, Hunan 410013, P.R. China.

Institute of Pathology Research, Department of Pathology, Xiangnan University, Chenzhou, Hunan 423000, P.R. China.

出版信息

Oncol Rep. 2015 Jul;34(1):111-20. doi: 10.3892/or.2015.3952. Epub 2015 May 5.

Abstract

The overall goal of the present study was to find and validate unidentified miRNAs that regulate epithelial-mesenchymal transition (EMT) and proliferation in ovarian cancer. Furthermore, we demonstrate that the high expression of miR-153 in human epithelial ovarian cancer (EOC) is associated with better survival. The mean expression level of miR-153 in ovarian cancer was significantly lower than in the adjacent carcinoma tissue. In the present study, we report that miR-153 are negative regulators of SET7 and ZEB2, miR-153 regulates SET7/ZEB2 expression and promotes SET7/ZEB2 mRNA degradation. Further, confirmed by reporter assays, SET7/ZEB2 are downstream targets of miR-153 directly bound to the 3' untranslated region (3'-UTR). Clone formation and wound-healing assay as well as Transwell assay proved that silencing of SET7 or ZEB2 partially abolished the enhancement of cell proliferation and invasion induced by downregulated miR-153. SET7 and ZEB2 are negatively correlated with miR-153 expression in human ovarian cancer and indicated a worse survival. Considering the role of SET7 and ZEB2 in EOC, it is important to clarify how the expression of SET7 and ZEB2 are regulated. Based on our results miR-153 inhibits proliferation and suppresses EMT and the invasive potential of ovarian cancer cells through downregulation of SET7 and ZEB2, supporting the pursuit of miR-153 as a potential target for ovarian cancer intervention.

摘要

本研究的总体目标是寻找并验证调控卵巢癌上皮-间质转化(EMT)和增殖的未知微小RNA(miRNA)。此外,我们证明了miR-153在人上皮性卵巢癌(EOC)中的高表达与更好的生存率相关。卵巢癌中miR-153的平均表达水平显著低于相邻癌组织。在本研究中,我们报告miR-153是SET7和ZEB2的负调节因子,miR-153调节SET7/ZEB2的表达并促进SET7/ZEB2 mRNA的降解。此外,报告基因检测证实,SET7/ZEB2是直接与3'非翻译区(3'-UTR)结合的miR-153的下游靶标。克隆形成、伤口愈合试验以及Transwell试验证明,SET7或ZEB2的沉默部分消除了下调miR-153诱导的细胞增殖和侵袭增强。SET7和ZEB2与人类卵巢癌中miR-153的表达呈负相关,且提示生存率较差。考虑到SET7和ZEB2在EOC中的作用,阐明SET7和ZEB2的表达如何被调控很重要。基于我们的结果,miR-153通过下调SET7和ZEB2抑制卵巢癌细胞的增殖、抑制EMT及侵袭潜能,支持将miR-153作为卵巢癌干预的潜在靶点进行研究。

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