Genome-wide transcriptional profiling reveals microRNA-correlated genes and biological processes in human lymphoblastoid cell lines

Liang Wang, Ann L Oberg, Yan Asmann, Hugues Sicotte, Shannon K. McDonnell, Shaun M. Riska, Wanguo Liu, Clifford J. Steer, Subbaya Subramanian, Julie M Cunningham, James R Cerhan, Stephen N Thibodeau

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

Background: Expression level of many genes shows abundant natural variation in human populations. The variations in gene expression are believed to contribute to phenotypic differences. Emerging evidence has shown that microRNAs (miRNAs) are one of the key regulators of gene expression. However, past studies have focused on the miRNA target genes and used loss- or gain-of-function approach that may not reflect natural association between miRNA and mRNAs. Methodology/Principal Findings: To examine miRNA regulatory effect on global gene expression under endogenous condition, we performed pair-wise correlation coefficient analysis on expression levels of 366 miRNAs and 14,174 messenger RNAs (mRNAs) in 90 immortalized lymphoblastoid cell lines, and observed significant correlations between the two species of RNA transcripts. We identified a total of 7,207 significantly correlated miRNA-mRNA pairs (false discovery rate q<0.01). Of those, 4,085 pairs showed positive correlations while 3,122 pairs showed negative correlations. Gene ontology analyses on the miRNA-correlated genes revealed significant enrichments in several biological processes related to cell cycle, cell communication and signal transduction. Individually, each of three miRNAs (miR-331, -98 and -33b) demonstrated significant correlation with the genes in cell cycle-related biological processes, which is consistent with important role of miRNAs in cell cycle regulation. Conclusions/Significance: This study demonstrates feasibility of using naturally expressed transcript profiles to identify endogenous correlation between miRNA and miRNA. By applying this genome-wide approach, we have identified thousands of miRNA-correlated genes and revealed potential role of miRNAs in several important cellular functions. The study results along with accompanying data sets will provide a wealth of high-throughput data to further evaluate the miRNA-regulated genes and eventually in phenotypic variations of human populations.

Original languageEnglish (US)
Article numbere5878
JournalPLoS One
Volume4
Issue number6
DOIs
StatePublished - Jun 11 2009

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Biological Phenomena
human cell lines
MicroRNAs
microRNA
Genes
Cells
Genome
Cell Line
genome
genes
messenger RNA
Gene expression
cell cycle
Gene Expression
human population
gene expression
Messenger RNA
Cell Cycle
cdc Genes
Signal transduction

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Genome-wide transcriptional profiling reveals microRNA-correlated genes and biological processes in human lymphoblastoid cell lines. / Wang, Liang; Oberg, Ann L; Asmann, Yan; Sicotte, Hugues; McDonnell, Shannon K.; Riska, Shaun M.; Liu, Wanguo; Steer, Clifford J.; Subramanian, Subbaya; Cunningham, Julie M; Cerhan, James R; Thibodeau, Stephen N.

In: PLoS One, Vol. 4, No. 6, e5878, 11.06.2009.

Research output: Contribution to journalArticle

Wang, Liang ; Oberg, Ann L ; Asmann, Yan ; Sicotte, Hugues ; McDonnell, Shannon K. ; Riska, Shaun M. ; Liu, Wanguo ; Steer, Clifford J. ; Subramanian, Subbaya ; Cunningham, Julie M ; Cerhan, James R ; Thibodeau, Stephen N. / Genome-wide transcriptional profiling reveals microRNA-correlated genes and biological processes in human lymphoblastoid cell lines. In: PLoS One. 2009 ; Vol. 4, No. 6.
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AU - Asmann, Yan

AU - Sicotte, Hugues

AU - McDonnell, Shannon K.

AU - Riska, Shaun M.

AU - Liu, Wanguo

AU - Steer, Clifford J.

AU - Subramanian, Subbaya

AU - Cunningham, Julie M

AU - Cerhan, James R

AU - Thibodeau, Stephen N

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AB - Background: Expression level of many genes shows abundant natural variation in human populations. The variations in gene expression are believed to contribute to phenotypic differences. Emerging evidence has shown that microRNAs (miRNAs) are one of the key regulators of gene expression. However, past studies have focused on the miRNA target genes and used loss- or gain-of-function approach that may not reflect natural association between miRNA and mRNAs. Methodology/Principal Findings: To examine miRNA regulatory effect on global gene expression under endogenous condition, we performed pair-wise correlation coefficient analysis on expression levels of 366 miRNAs and 14,174 messenger RNAs (mRNAs) in 90 immortalized lymphoblastoid cell lines, and observed significant correlations between the two species of RNA transcripts. We identified a total of 7,207 significantly correlated miRNA-mRNA pairs (false discovery rate q<0.01). Of those, 4,085 pairs showed positive correlations while 3,122 pairs showed negative correlations. Gene ontology analyses on the miRNA-correlated genes revealed significant enrichments in several biological processes related to cell cycle, cell communication and signal transduction. Individually, each of three miRNAs (miR-331, -98 and -33b) demonstrated significant correlation with the genes in cell cycle-related biological processes, which is consistent with important role of miRNAs in cell cycle regulation. Conclusions/Significance: This study demonstrates feasibility of using naturally expressed transcript profiles to identify endogenous correlation between miRNA and miRNA. By applying this genome-wide approach, we have identified thousands of miRNA-correlated genes and revealed potential role of miRNAs in several important cellular functions. The study results along with accompanying data sets will provide a wealth of high-throughput data to further evaluate the miRNA-regulated genes and eventually in phenotypic variations of human populations.

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