Xu Xue, Xu Yongcan, Shi Chuanqin, Wang Baoyu, Yu Xiang, Zou Yanfen, Hu Tao
Department of Immunology, Binzhou Medical College, Yantai 264003, China.
Department of General Surgery, Huzhou Central Hospital, Huzhou 313000, China.
Oncotarget. 2017 Sep 23;8(50):87773-87781. doi: 10.18632/oncotarget.21206. eCollection 2017 Oct 20.
Recently, a growing number of studies have indicated that long noncoding RNAs (lncRNAs) are emerging as new critical regulators of tumorigenesis and prognostic markers in multiple cancers. However, the expression pattern of lncRNAs and their contributions in renal cell carcinoma (RCC) remains poorly understood. In this study, we performed a genome-wide comprehensively analysis of lncRNAs profiling and clinical relevance to provide valuable lncRNA candidates for the further study in RCC. RCC and non-tumor tissues RNA sequencing data, and microarray data were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), then, these data were annotated and analyzed to find dysregulated lncRNAs in RCC. We identified that hundreds of lncRNAs were differentially expressed in RCC tissues compared with normal tissues, and genomic variation analyses revealed that copy number amplification or deletion happened in some of these lncRNAs genome loci. Moreover, lots of lncRNAs expression levels are significantly associated RCC patients overall survival time, such as PVT1 and DUXAP8. Finally, we identified some novel metastasis associated lncRNAs in RCC (such as DUXAP8) by analyzing lncRNAs profiling in the RCC tissues from patients with metastasis compared with the primary RCC tissues without metastasis; knockdown of DUXAP8 could impair RCC cells invasive ability . Overall, our findings illuminate a lot of lncRNAs are aberrantly expressed in RCC that may offer useful resource for identification novel prognostic markers in this disease.
最近,越来越多的研究表明,长链非编码RNA(lncRNAs)正成为多种癌症中肿瘤发生的新关键调节因子和预后标志物。然而,lncRNAs在肾细胞癌(RCC)中的表达模式及其作用仍知之甚少。在本研究中,我们对lncRNAs图谱和临床相关性进行了全基因组综合分析,为RCC的进一步研究提供有价值的lncRNA候选物。从癌症基因组图谱(TCGA)和基因表达综合数据库(GEO)获取RCC和非肿瘤组织的RNA测序数据及微阵列数据,然后对这些数据进行注释和分析,以发现RCC中失调的lncRNAs。我们发现,与正常组织相比,数百种lncRNAs在RCC组织中差异表达,基因组变异分析显示其中一些lncRNAs基因组位点发生了拷贝数扩增或缺失。此外,许多lncRNAs的表达水平与RCC患者的总生存时间显著相关,如PVT1和DUXAP8。最后,通过分析转移患者的RCC组织与无转移的原发性RCC组织中的lncRNAs图谱,我们在RCC中鉴定出一些新发现的与转移相关的lncRNAs(如DUXAP8);敲低DUXAP8可损害RCC细胞的侵袭能力。总体而言,我们的研究结果表明许多lncRNAs在RCC中异常表达,这可能为识别该疾病的新预后标志物提供有用资源。