Chang, Li, Yuan, Wang, Wen (2019) LINC00997, a novel long noncoding RNA, contributes to metastasis via regulation of S100A11 in kidney renal clear cell carcinoma The international journal of biochemistry & cell biology () 105590

Abstract

Long noncoding RNAs (lncRNAs) play an essential role in cancer development. However, the contribution of the lncRNA LINC00997 to kidney renal clear cell carcinoma (KIRC) has not been thoroughly elucidated to date. In this study, we examined the expression and biological effect of LINC00997 in KIRC development. We also investigated the potential mechanism underlying the observed effects. We found that LINC00997 is highly expressed in multiple carcinomas, being highest in stage IV KIRC in our RNA-Seq datasets. In addition, our data demonstrated that in KIRC patients, higher levels of LINC00997 are correlated with lower overall survival (OS) and disease-free survival (DFS) rates. In 18 cases of KIRC, we found that LINC00997 expression was greater in cancer tissues and metastases than in normal tissues. These results revealed that S100A11 is positively associated with LINC00997 in KIRC, which is positively correlated with metastasis-associated molecules VIM, MMP2 and MMP7. Our in vitro wound healing assay and Transwell tests demonstrated that interfering with either LINC00997 or S100A11 expression reduced migration of 786-O cells by inhibiting VIM, MMP2 and MMP7 expression. Importantly, we verified LINC00997 and STAT3 binding by RIP and determined that both LINC00997 and STAT3 bind to the S100A11 promoter, as shown by dual-luciferase reporter gene assay. In addition, inhibiting LINC00997 or STAT3 expression attenuated S100A11 levels. Consequently, the LINC00997-STAT3-S100A11 axis may promote the development of KIRC, and LINC00997 may represent a potential prognostic biomarker and therapeutic target for KIRC patients. Copyright © 2019. Published by Elsevier Ltd.

长非编码RNA(lncRNA)在癌症发展中起重要作用。然而,迄今尚未充分阐明lncRNA LINC00997对肾肾透明细胞癌(KIRC)的贡献。在这项研究中,我们检查了LINC00997在KIRC发展中的表达和生物学效应。我们还研究了观察到的影响的潜在机制。我们发现LINC00997在多种癌中高表达,在我们的RNA-Seq数据集中在IV期KIRC中最高。此外,我们的数据表明,在KIRC患者中,较高水平的LINC00997与较低的总生存期(OS)和无病生存期(DFS)相关。在18例KIRC中,我们发现LINC00997在癌组织和转移灶中的表达高于正常组织。这些结果显示S100A11与KIRC中的LINC00997呈正相关,与转移相关分子VIM,MMP2和MMP7呈正相关。我们的体外伤口愈合测定和Transwell测试表明干扰LINC00997或S100A11表达通过抑制VIM,MMP2和MMP7表达减少了786-O细胞的迁移。重要的是,我们通过RIP验证了LINC00997和STAT3的结合,并确定LINC00997和STAT3都与S100A11启动子结合,如双荧光素酶报告基因测定所示。此外,抑制LINC00997或STAT3表达会减弱S100A11的水平。因此,LINC00997-STAT3-S100A11轴可能促进KIRC的发展,LINC00997可能代表KIRC患者的潜在预后生物标志物和治疗靶点。版权所有©2019。由Elsevier Ltd.出版

Links

http://www.ncbi.nlm.nih.gov/pubmed/31442606
http://dx.doi.org/10.1016/j.biocel.2019.105590

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