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      Integrated Profiling of MicroRNAs and mRNAs: MicroRNAs Located on Xq27.3 Associate with Clear Cell Renal Cell Carcinoma

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          Abstract

          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.

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          Most cited references41

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          Cancer genes and the pathways they control.

          Bert Vogelstein, Kenneth W. Kinzler (2004)
          The revolution in cancer research can be summed up in a single sentence: cancer is, in essence, a genetic disease. In the last decade, many important genes responsible for the genesis of various cancers have been discovered, their mutations precisely identified, and the pathways through which they act characterized. The purposes of this review are to highlight examples of progress in these areas, indicate where knowledge is scarce and point out fertile grounds for future investigation.
          Article 0 comments Cited 953 times – based on 0 reviews     Review now
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            An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans.

            N. Lau, L. P. Lim, E G Weinstein … (2001)
            Two small temporal RNAs (stRNAs), lin-4 and let-7, control developmental timing in Caenorhabditis elegans. We find that these two regulatory RNAs are members of a large class of 21- to 24-nucleotide noncoding RNAs, called microRNAs (miRNAs). We report on 55 previously unknown miRNAs in C. elegans. The miRNAs have diverse expression patterns during development: a let-7 paralog is temporally coexpressed with let-7; miRNAs encoded in a single genomic cluster are coexpressed during embryogenesis; and still other miRNAs are expressed constitutively throughout development. Potential orthologs of several of these miRNA genes were identified in Drosophila and human genomes. The abundance of these tiny RNAs, their expression patterns, and their evolutionary conservation imply that, as a class, miRNAs have broad regulatory functions in animals.
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              MicroRNA biogenesis: coordinated cropping and dicing.

              V Kim (2005)
              The recent discovery of microRNAs (miRNAs) took many by surprise because of their unorthodox features and widespread functions. These tiny, approximately 22-nucleotide, RNAs control several pathways including developmental timing, haematopoiesis, organogenesis, apoptosis, cell proliferation and possibly even tumorigenesis. Among the most pressing questions regarding this unusual class of regulatory miRNA-encoding genes is how miRNAs are produced in cells and how the genes themselves are controlled by various regulatory networks.
              Article 0 comments Cited 713 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                : Role: Editor
                Journal
                Journal ID (nlm-ta): PLoS One
                Journal ID (publisher-id): plos
                Journal ID (pmc): plosone
                Title: PLoS ONE
                Publisher: Public Library of Science (San Francisco, USA )
                ISSN (Electronic): 1932-6203
                Publication date Collection: 2010
                Publication date (Electronic): 30 December 2010
                Volume: 5
                Issue: 12
                Electronic Location Identifier: e15224
                Affiliations
                [1 ]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
                [2 ]Beijing Genomics Institute at Shenzhen, Shenzhen, China
                [3 ]School of Bioscience and Biotechnology, South China University of Technology, Guangzhou, China
                [4 ]Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China
                [5 ]Graduate University of Chinese Academy of Sciences, Beijing, China
                [6 ]Department of Urosurgery, The Second Hospital of Central-Southern University, Changsha, China
                [7 ]Department of Urosurgery, The First Hospital of Anhui Medical University, Hefei, China
                [8 ]Shantou University Medical College, Shantou, China
                Baylor College of Medicine, United States of America
                Author notes

                Conceived and designed the experiments: LZ JH ZL XL XH ZC X. Zhang HY. Performed the experiments: LZ XH MS XX FS QZ. Analyzed the data: Jiahao Chen ZL YH MC ZH ZP. Contributed reagents/materials/analysis tools: XL X. Zhao CL YW LS Jing Chen ZZ RY JY ZG. Wrote the paper: LZ Jiahao Chen ZL XH. Designed the project and gave final approval of the version to be published: LZ YG JW ZC X. Zhang HY.

                Article
                Publisher ID: PONE-D-10-00282
                DOI: 10.1371/journal.pone.0015224
                PMC ID: 3013074
                PubMed ID: 21253009
                SO-VID: 1aed2847-5965-4844-b581-502d3b84a256
                Copyright © Zhou et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                History
                Date received : 4 August 2010
                Date accepted : 1 November 2010
                Page count
                Pages: 10
                Categories
                Subject: Research Article
                Subject: Biology
                Subject: Biochemistry
                Subject: Nucleic Acids
                Subject: RNA
                Subject: Computational Biology
                Subject: Genomics
                Subject: Genome Analysis Tools
                Subject: Transcriptomes
                Subject: Genome Expression Analysis
                Subject: Genomics
                Subject: Genomic Medicine
                Subject: Molecular Cell Biology
                Subject: Medicine
                Subject: Oncology
                Subject: Cancers and Neoplasms
                Subject: Genitourinary Tract Tumors
                Subject: Renal Cell Carcinoma
                Subject: Surgery
                Subject: Urology

                ScienceOpen disciplines: Uncategorized
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                ScienceOpen disciplines: Uncategorized

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