Department of Colorectal Surgery, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Department of Prosthodontics, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Int J Biochem Cell Biol. 2019 Nov;116:105590. doi: 10.1016/j.biocel.2019.105590. Epub 2019 Aug 20.
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.
长链非编码 RNA（lncRNA）在癌症发展中发挥着重要作用。然而，迄今为止，lncRNA LINC00997 对肾透明细胞癌（KIRC）的贡献尚未得到彻底阐明。在本研究中，我们研究了 LINC00997 在 KIRC 发展中的表达和生物学效应。我们还探讨了观察到的效应的潜在机制。我们发现 LINC00997 在多种癌中高度表达，在我们的 RNA-Seq 数据集中，在 IV 期 KIRC 中表达最高。此外，我们的数据表明，在 KIRC 患者中，LINC00997 水平越高，总生存率（OS）和无病生存率（DFS）越低。在 18 例 KIRC 中，我们发现 LINC00997 的表达在癌症组织和转移灶中高于正常组织。这些结果表明，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。我们的体外划痕愈合试验和 Transwell 试验表明，干扰 LINC00997 或 S100A11 的表达通过抑制 VIM、MMP2 和 MMP7 的表达，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，并通过双荧光素酶报告基因试验确定 LINC00997 和 STAT3 均结合到 S100A11 启动子上。此外，抑制 LINC00997 或 STAT3 的表达减弱了 S100A11 的水平。因此，LINC00997-STAT3-S100A11 轴可能促进 KIRC 的发展，LINC00997 可能代表 KIRC 患者潜在的预后生物标志物和治疗靶点。
