Zhang Hai-Min, Yang Feng-Qiang, Yan Yang, Che Jian-Ping, Zheng Jun-Hua
Department of Urology, Shanghai Tenth People's Hospital, Tongji University Shanghai 200072, China.
Int J Clin Exp Pathol. 2014 Aug 15;7(9):5801-9. eCollection 2014.
Long non-coding RNAs (lncRNAs) play a key role in cellular processes, such as cell growth, apoptosis, and carcinogenesis. lncRNAs SPRY4-IT1 has recently been identified to be involved in tumorigenesis of several cancers such as non-small cell lung cancer and esophageal squamous cell carcinoma. However, the role of SPRY4-IT1 in clear cell renal cell carcinoma (ccRCC) remains unclear.
The expression of SPRY4-IT1 was examined in ccRCC patients and renal cancer cell lines by using quantitative real-time PCR (qRT-PCR). The relationship between SPRY4-IT1 level and clinicopathological parameters of ccRCC was analyzed with the Kaplan-Meier method and Cox proportional hazards model. Small interfering RNA (siRNA) was used to suppress SPRY4-IT1 expression in renal cancer cell line 786-O. In vitro assays were performed to further explore its role in renal cancer progressio.
The relative level of SPRY4-IT1 was significantly higher in ccRCC tissues compared to the adjacent normal renal tissues. And higher expression of SPRY4-IT1 was found in renal cancer cell lines compared with the normal human proximal tubule epithelial cell line HK-2. The ccRCC patients with higher SPRY4-IT1 expression had an advanced clinical stage and poorer prognosis than those with lower SPRY4-IT1 expression. Multivariate analyses by Cox's proportional hazard model revealed that expression of SPRY4-IT1 was an independent prognostic factor in ccRCC. In vitro assays, our results indicated that knockdown of SPRY4-IT1 reduced renal cancer cell proliferation, migration, and invasion.
Our data suggested that lncRNA SPRY4-IT1 might be considered as a potential prognostic indicator and a potential target for therapeutic intervention in RC.
长链非编码RNA(lncRNAs)在细胞生长、凋亡和致癌作用等细胞过程中发挥关键作用。最近已确定lncRNAs SPRY4-IT1参与了几种癌症的肿瘤发生,如非小细胞肺癌和食管鳞状细胞癌。然而,SPRY4-IT1在透明细胞肾细胞癌(ccRCC)中的作用仍不清楚。
采用定量实时PCR(qRT-PCR)检测ccRCC患者和肾癌细胞系中SPRY4-IT1的表达。用Kaplan-Meier法和Cox比例风险模型分析SPRY4-IT1水平与ccRCC临床病理参数之间的关系。使用小干扰RNA(siRNA)抑制肾癌细胞系786-O中SPRY4-IT1的表达。进行体外实验以进一步探讨其在肾癌进展中的作用。
与相邻正常肾组织相比,ccRCC组织中SPRY4-IT1的相对水平显著更高。与正常人近端肾小管上皮细胞系HK-2相比,肾癌细胞系中SPRY4-IT1的表达更高。SPRY4-IT1表达较高的ccRCC患者比SPRY4-IT1表达较低的患者临床分期更晚,预后更差。Cox比例风险模型的多变量分析显示,SPRY4-IT1的表达是ccRCC的独立预后因素。在体外实验中,我们的结果表明敲低SPRY4-IT1可降低肾癌细胞的增殖、迁移和侵袭。
我们的数据表明lncRNA SPRY4-IT1可能被视为一种潜在的预后指标以及肾癌治疗干预的潜在靶点。