title: The impact of microRNA expression on cellular proliferation.
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.
authors.affiliation: Section of Hematology/Oncology, Department of Medicine, The University of Chicago, 900 E 57th Street, KCBD, Chicago, IL, 60637, USA.
authors.forename: Divya
authors.initials: D
authors.lastname: Lenkala
authors.forename: Bonnie
authors.initials: B
authors.lastname: LaCroix
authors.forename: Eric R
authors.initials: ER
authors.lastname: Gamazon
authors.forename: Paul
authors.initials: P
authors.lastname: Geeleher
authors.forename: Hae Kyung
authors.initials: HK
authors.lastname: Im
authors.forename: R Stephanie
authors.initials: RS
authors.lastname: Huang
mesh_terms: D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D044383:Black People / Q000235:genetics; D027682:Cation Transport Proteins / Q000235:genetics; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005006:Ethnicity; D005060:Europe; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055106:Genome-Wide Association Study; D060148:HapMap Project; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D024101:Mitochondrial Proteins / Q000235:genetics; D009549:Nigeria; D010051:Ovarian Neoplasms / Q000235:genetics; D010641:Phenotype; D012044:Regression Analysis; D025521:Tumor Suppressor Proteins / Q000235:genetics; D044465:White People / Q000235:genetics
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D027682:Cation Transport Proteins; D035683:MicroRNAs; D024101:Mitochondrial Proteins; D025521:Tumor Suppressor Proteins; C079440:MXI1 protein, human; C561492:Slc25a37 protein, human