马拉特1
基因沉默
癌症研究
长非编码RNA
EZH2型
癌变
生物
下调和上调
细胞凋亡
癌症
表观遗传学
分子生物学
基因
遗传学
作者
Hiroshi Hirata,Yuji Hinoda,Varahram Shahryari,Guoren Deng,Koji Nakajima,Z. Laura Tabatabai,Nobuhisa Ishii,Rajvir Dahiya
标识
DOI:10.1158/0008-5472.c.6507656
摘要
<div>Abstract<p>Recently, long noncoding RNAs (lncRNA) have emerged as new gene regulators and prognostic markers in several cancers, including renal cell carcinoma (RCC). In this study, we investigated the contributions of the lncRNA MALAT1 in RCC with a specific focus on its transcriptional regulation and its interactions with Ezh2 and miR-205. We found that MALAT1 expression was higher in human RCC tissues, where it was associated with reduced patient survival. MALAT1 silencing decreased RCC cell proliferation and invasion and increased apoptosis. Mechanistic investigations showed that MALAT1 was transcriptionally activated by c-Fos and that it interacted with Ezh2. After MALAT1 silencing, E-cadherin expression was increased, whereas β-catenin expression was decreased through Ezh2. Reciprocal interaction between MALAT1 and miR-205 was also observed. Lastly, MALAT1 bound Ezh2 and oncogenesis facilitated by MALAT1 was inhibited by Ezh2 depletion, thereby blocking epithelial–mesenchymal transition via E-cadherin recovery and β-catenin downregulation. Overall, our findings illuminate how overexpression of MALAT1 confers an oncogenic function in RCC that may offer a novel theranostic marker in this disease. <i>Cancer Res; 75(7); 1322–31. ©2015 AACR</i>.</p></div>
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