A Meta-Analysis: Identification of Common Mir-145 Target Genes that have Similar Behavior in Different GEO Datasets

PLoS One. 2016 Sep 21;11(9):e0161491. doi: 10.1371/journal.pone.0161491. eCollection 2016.

Abstract

Background: MicroRNAs, which are small regulatory RNAs, post-transcriptionally regulate gene expression by binding 3'-UTR of their mRNA targets. Their deregulation has been shown to cause increased proliferation, migration, invasion, and apoptosis. miR-145, an important tumor supressor microRNA, has shown to be downregulated in many cancer types and has crucial roles in tumor initiation, progression, metastasis, invasion, recurrence, and chemo-radioresistance. Our aim is to investigate potential common target genes of miR-145, and to help understanding the underlying molecular pathways of tumor pathogenesis in association with those common target genes.

Methods: Eight published microarray datasets, where targets of mir-145 were investigated in cell lines upon mir-145 over expression, were included into this study for meta-analysis. Inter group variabilities were assessed by box-plot analysis. Microarray datasets were analyzed using GEOquery package in Bioconducter 3.2 with R version 3.2.2 and two-way Hierarchical Clustering was used for gene expression data analysis.

Results: Meta-analysis of different GEO datasets showed that UNG, FUCA2, DERA, GMFB, TF, and SNX2 were commonly downregulated genes, whereas MYL9 and TAGLN were found to be commonly upregulated upon mir-145 over expression in prostate, breast, esophageal, bladder cancer, and head and neck squamous cell carcinoma. Biological process, molecular function, and pathway analysis of these potential targets of mir-145 through functional enrichments in PPI network demonstrated that those genes are significantly involved in telomere maintenance, DNA binding and repair mechanisms.

Conclusion: As a conclusion, our results indicated that mir-145, through targeting its common potential targets, may significantly contribute to tumor pathogenesis in distinct cancer types and might serve as an important target for cancer therapy.

Grant support

The research carried out in this manuscript is supported by grant number 210T009 supported by The Scientific and Technological Research Council of Turkey (TUBITAK). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.