Faculty Collaboration Database

Genome-wide transcriptional profiling reveals microRNA-correlated genes and biological processes in human lymphoblastoid cell lines. PLoS One 2009 Jun 11;4(6):e5878

Date

06/12/2009

Pubmed ID

19517021

Pubmed Central ID

PMC2691578

DOI

10.1371/journal.pone.0005878

Scopus ID

2-s2.0-67649989679 (requires institutional sign-in at Scopus site)   66 Citations

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.

Author List

Wang L, Oberg AL, Asmann YW, Sicotte H, McDonnell SK, Riska SM, Liu W, Steer CJ, Subramanian S, Cunningham JM, Cerhan JR, Thibodeau SN

MESH terms used to index this publication - Major topics in bold

Adult
Aged
Cell Line
Computational Biology
Gene Expression Profiling
Gene Expression Regulation
Genome-Wide Association Study
Humans
Lymphocytes
Male
MicroRNAs
Middle Aged
Oligonucleotide Array Sequence Analysis
RNA, Messenger
Transcription, Genetic