LINC00997, a novel long noncoding RNA, contributes to metastasis via regulation of S100A11 in kidney renal clear cell carcinoma
LINC00997, a novel long noncoding RNA, contributes to metastasis via regulation of S100A11 in kidney renal clear cell carcinoma
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DOI：
10.1016/j.biocel.2019.105590
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发表时间：
2019-11-01
影响因子：
4
通讯作者：
Wen, Jianguo
中科院分区：
文献类型：
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作者：
Chang, Yuan;Li, Na;Wen, Jianguo
长链非编码RNA（IncRNA）在癌症发展中起着重要作用。然而，IncRNA LINC 00997对肾透明细胞癌（KIRC）的贡献迄今尚未得到彻底阐明。在这项研究中，我们研究了LINC 00997在KIRC发展中的表达和生物学效应。我们还研究了所观察到的影响的潜在机制。我们发现LINC 00997在多种癌中高度表达，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LINC 00997与较低的总生存率（OS）和无病生存率（DFS）相关。在18例KIRC中，我们发现LINC 00997在癌组织和转移灶中的表达高于正常组织。这些结果表明，S100 A11与KIRC中的LINC 00997正相关，LINC 00997与转移相关分子Vim、MMP 2和MMP 7正相关。我们的体外伤口愈合试验和Transwell试验表明，干扰LINC 00997或S100 A11表达通过抑制Vim、MMP 2和MMP 7表达而减少786-O细胞的迁移。重要的是，我们通过RIP验证了LINC 00997和STAT 3的结合，并确定LINC 00997和STAT 3都与S100 A11启动子结合，如双荧光素酶报告基因测定所示。此外，抑制LINC 00997或STAT 3表达减弱了S100 A11水平。因此，LINC 00997-STAT 3-S100 A11轴可能促进KIRC的发展，LINC 00997可能代表KIRC患者的潜在预后生物标志物和治疗靶点。
Long noncoding RNAs (IncRNAs) play an essential role in cancer development. However, the contribution of the IncRNA 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.