The Key Laboratory of Stem Cell Biology, Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Institute of Urology, Peking University Shenzhen Hospital, Shenzhen PKU-HKUST Medical Center, Shenzhen, China.
PLoS One. 2010 Dec 30;5(12):e15224. doi: 10.1371/journal.pone.0015224.
With the advent of second-generation sequencing, the expression of gene transcripts can be digitally measured with high accuracy. The purpose of this study was to systematically profile the expression of both mRNA and miRNA genes in clear cell renal cell carcinoma (ccRCC) using massively parallel sequencing technology.
The expression of mRNAs and miRNAs were analyzed in tumor tissues and matched normal adjacent tissues obtained from 10 ccRCC patients without distant metastases. In a prevalence screen, some of the most interesting results were validated in a large cohort of ccRCC patients.
A total of 404 miRNAs and 9,799 mRNAs were detected to be differentially expressed in the 10 ccRCC patients. We also identified 56 novel miRNA candidates in at least two samples. In addition to confirming that canonical cancer genes and miRNAs (including VEGFA, DUSP9 and ERBB4; miR-210, miR-184 and miR-206) play pivotal roles in ccRCC development, promising novel candidates (such as PNCK and miR-122) without previous annotation in ccRCC carcinogenesis were also discovered in this study. Pathways controlling cell fates (e.g., cell cycle and apoptosis pathways) and cell communication (e.g., focal adhesion and ECM-receptor interaction) were found to be significantly more likely to be disrupted in ccRCC. Additionally, the results of the prevalence screen revealed that the expression of a miRNA gene cluster located on Xq27.3 was consistently downregulated in at least 76.7% of ∼50 ccRCC patients.
Our study provided a two-dimensional map of the mRNA and miRNA expression profiles of ccRCC using deep sequencing technology. Our results indicate that the phenotypic status of ccRCC is characterized by a loss of normal renal function, downregulation of metabolic genes, and upregulation of many signal transduction genes in key pathways. Furthermore, it can be concluded that downregulation of miRNA genes clustered on Xq27.3 is associated with ccRCC.
随着第二代测序技术的出现，基因转录本的表达可以高精度地进行数字化测量。本研究的目的是使用大规模平行测序技术系统地分析透明细胞肾细胞癌（ccRCC）中 mRNA 和 miRNA 基因的表达。
从 10 例无远处转移的 ccRCC 患者的肿瘤组织和配对的正常相邻组织中分析 mRNA 和 miRNA 的表达。在患病率筛查中，在大量 ccRCC 患者中验证了一些最有趣的结果。
在 10 例 ccRCC 患者中，共检测到 404 个 miRNA 和 9799 个 mRNA 差异表达。我们还在至少两个样本中鉴定了 56 个新的 miRNA 候选物。除了证实经典的癌症基因和 miRNA（包括 VEGFA、DUSP9 和 ERBB4；miR-210、miR-184 和 miR-206）在 ccRCC 发展中发挥关键作用外，在这项研究中还发现了一些以前在 ccRCC 癌变中没有注释的有前途的候选物（如 PNCK 和 miR-122）。控制细胞命运（如细胞周期和细胞凋亡途径）和细胞通讯（如粘着斑和 ECM-受体相互作用）的途径被发现更有可能在 ccRCC 中被破坏。此外，患病率筛查的结果表明，位于 Xq27.3 上的 miRNA 基因簇的表达在至少 76.7%的约 50 例 ccRCC 患者中持续下调。
本研究使用深度测序技术为 ccRCC 的 mRNA 和 miRNA 表达谱提供了二维图谱。我们的结果表明，ccRCC 的表型状态的特征是正常肾功能丧失、代谢基因下调以及关键途径中许多信号转导基因上调。此外，可以得出结论，位于 Xq27.3 上的 miRNA 基因簇的下调与 ccRCC 相关。
