Integrated profiling of microRNAs and mRNAs: microRNAs located on Xq27.3 associate with clear cell renal cell carcinoma.
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.


METHODS
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.


RESULTS
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.
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.
Liang
L
Zhou
Jiahao
J
Chen
Zhizhong
Z
Li
Xianxin
X
Li
Xueda
X
Hu
Yi
Y
Huang
Xiaokun
X
Zhao
Chaozhao
C
Liang
Yong
Y
Wang
Liang
L
Sun
Min
M
Shi
Xiaohong
X
Xu
Feng
F
Shen
Maoshan
M
Chen
Zujing
Z
Han
Zhiyu
Z
Peng
Qingna
Q
Zhai
Jing
J
Chen
Zhongfu
Z
Zhang
Ruilin
R
Yang
Jiongxian
J
Ye
Zhichen
Z
Guan
Huanming
H
Yang
Yaoting
Y
Gui
Jun
J
Wang
Zhiming
Z
Cai
Xiuqing
X
Zhang
D017209:Apoptosis; D002292:Carcinoma, Renal Cell / Q000235:genetics*; D002453:Cell Cycle; D041321:Chromosomes, Human, X; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics*; D008957:Models, Genetic; D015233:Models, Statistical; D009362:Neoplasm Metastasis; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D015203:Reproducibility of Results
D035683:MicroRNAs; D012333:RNA, Messenger
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