Open AccessIntegrated Profiling of MicroRNAs and mRNAs: MicroRNAs Located on Xq27.3 Associate with Clear Cell Renal Cell Carcinoma
Author(s) -
Liang Zhou,
Jiahao Chen,
Zhizhong Li,
Xianxin Li,
Xueda Hu,
Yi Huang,
Xiaokun Zhao,
Chaozhao Liang,
Yong Wang,
Liang Sun,
Min Shi,
Xiaohong Xu,
Feng Shen,
Maoshan Chen,
Zujing Han,
Zhiyu Peng,
Qian Zhai,
Jing Chen,
Zhang Zhong-fu,
Ruining Yang,
Jiongxian Ye,
Zhiyong Guan,
Huanming Yang,
Yaoting Gui,
Jun Wang,
Zhiming Cai,
Xiuqing Zhang
Publication year - 2010
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0015224
Subject(s) - microrna , clear cell renal cell carcinoma , biology , carcinogenesis , gene expression profiling , cell growth , cancer research , gene expression , cell cycle , cell , gene , renal cell carcinoma , genetics , pathology , medicine
Background 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. Methodology 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. Principal Findings 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. Conclusions 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.