Department of Urology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
Department of Urology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China.
Cell Death Dis. 2021 Jul 9;12(7):689. doi: 10.1038/s41419-021-03955-7.
Renal cell carcinoma is the second malignant tumors in the urinary system with high mortality and morbidity. Increasing evidence suggests that long non-coding RNAs (lncRNAs) play critical roles in tumor development and progression. In the current study, based on the publicly available data obtained from GEO and TCGA database, we identified five prognosis-related lncRNAs with the ability to predict the prognosis of patients with renal cell carcinoma. Among them, the uncharacterized and upregulated lncRNA RCAT1 (renal cancer-associated transcript 1) was identified as the key lncRNA. Our data further revealed that the expression of lncRNA RCAT1 was significantly upregulated in renal cell carcinoma tissues and cells. Gain-of-function and loss-of-function studies showed that lncRNA RCAT1 promoted cell proliferation, migration, and invasion in vitro and in vivo. Furthermore, we verified that lncRNA RCAT1 could abundantly sponge miR-214-5p, which served as a tumor suppressor in renal cell carcinoma. Significantly, miR-214-5p overexpression could attenuate the promotion of cell proliferation and metastasis induced by lncRNA RCAT1. Moreover, we found that E2F2 was a direct target of miR-214-5p, and lncRNA RCAT1 could protect E2F2 from miR-214-5p-mediated degradation. Taken together, our findings suggested that lncRNA RCAT1 could enhance the malignant phenotype of renal cell carcinoma cells by modulating miR-214-5p/E2F2 axis, and lncRNA RCAT1 might be a novel prognostic biomarker and a potential therapeutic target for renal cell carcinoma.
肾细胞癌是泌尿系统第二大恶性肿瘤，死亡率和发病率均较高。越来越多的证据表明，长链非编码 RNA（lncRNA）在肿瘤的发生和发展中起着关键作用。在本研究中，我们基于从 GEO 和 TCGA 数据库获得的公开数据，鉴定出了 5 个与肾细胞癌患者预后相关的 lncRNA，这些 lncRNA 具有预测肾细胞癌患者预后的能力。其中，未被描述且上调的 lncRNA RCAT1（肾癌相关转录本 1）被鉴定为关键 lncRNA。我们的数据进一步表明，lncRNA RCAT1 在肾细胞癌组织和细胞中的表达显著上调。功能获得和功能丧失研究表明，lncRNA RCAT1 可促进体外和体内肾癌细胞的增殖、迁移和侵袭。此外，我们验证了 lncRNA RCAT1 可以大量吸附 miR-214-5p，miR-214-5p 在肾细胞癌中作为肿瘤抑制因子发挥作用。重要的是，miR-214-5p 的过表达可以减弱 lncRNA RCAT1 诱导的细胞增殖和转移的促进作用。此外，我们发现 E2F2 是 miR-214-5p 的直接靶标，lncRNA RCAT1 可以保护 E2F2 免受 miR-214-5p 介导的降解。总之，我们的研究结果表明，lncRNA RCAT1 通过调节 miR-214-5p/E2F2 轴，增强肾细胞癌细胞的恶性表型，lncRNA RCAT1 可能成为肾细胞癌的一种新的预后标志物和潜在的治疗靶点。
