The impact of microRNA expression on cellular proliferation

Hum Genet. 2014 Jul;133(7):931-8. doi: 10.1007/s00439-014-1434-4. Epub 2014 Mar 8.

Abstract

As an important class of non-coding regulatory RNAs, microRNAs (miRNAs) play a key role in a range of biological processes. These molecules serve as post-transcriptional regulators of gene expression and their regulatory activity has been implicated in disease pathophysiology and pharmacological traits. We sought to investigate the impact of miRNAs on cellular proliferation to gain insight into the molecular basis of complex traits that depend on cellular growth, including, most prominently, cancer. We examined the relationship between miRNA expression and intrinsic cellular growth (iGrowth) in the HapMap lymphoblastoid cell lines derived from individuals of different ethnic backgrounds. We found a substantial enrichment for miRNAs (53 miRNAs, FDR < 0.05) correlated with cellular proliferation in pooled CEU (Caucasian of northern and western European descent) and YRI (individuals from Ibadan, Nigeria) samples. Specifically, 119 miRNAs (59 %) were significantly correlated with iGrowth in YRI; of these miRNAs, 18 were correlated with iGrowth in CEU. To gain further insight into the effect of miRNAs on cellular proliferation in cancer, we showed that over-expression of miR-22, one of the top iGrowth-associated miRNAs, leads to growth inhibition in an ovarian cancer cell line (SKOV3). Furthermore, over-expression of miR-22 down-regulates the expression of its target genes (MXI1 and SLC25A37) in this ovarian cancer cell line, highlighting an miRNA-mediated regulatory network potentially important for cellular proliferation. Importantly, our study identified miRNAs that can be used as molecular targets in cancer therapy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Black People / genetics
  • Cation Transport Proteins / genetics
  • Cell Line, Transformed
  • Cell Line, Tumor
  • Cell Proliferation*
  • Ethnicity
  • Europe
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Genome-Wide Association Study
  • HapMap Project
  • Humans
  • MicroRNAs / genetics*
  • Mitochondrial Proteins / genetics
  • Nigeria
  • Ovarian Neoplasms / genetics
  • Phenotype
  • Regression Analysis
  • Tumor Suppressor Proteins / genetics
  • White People / genetics

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Cation Transport Proteins
  • MXI1 protein, human
  • MicroRNAs
  • Mitochondrial Proteins
  • Slc25a37 protein, human
  • Tumor Suppressor Proteins