Screening of Differently Expressed miRNA and mRNA in Prostate Cancer by Integrated Analysis of Transcription Data

doi:10.1016/j.urology.2016.04.041

Urology

Volume 94, August 2016, Pages 313.e1-313.e6

https://doi.org/10.1016/j.urology.2016.04.041 Get rights and content

Objective

The purpose of this study was to screen aberrantly expressed miRNAs and genes in prostate cancer (PCA), and further uncover the underlying mechanisms for the development of PCA.

Materials and Methods

We searched the Gene Expression Omnibus database for miRNA and gene expression datasets of PCA, and then separately integrated miRNA and gene expression datasets to identify miRNA and gene expression profiles in PCA. Target genes of differentially expressed miRNAs were predicted through miRWalk database. We matched these target genes with the list of differentially expressed genes to identify miRNA-target gene pairs whose expression was inversely correlated. The function of these target genes was annotated.

Results

Twenty-nine differentially expressed miRNAs and 946 differentially expressed genes were identified between PCA and normal control. Seven hundred fifty-one miRNA-target gene pairs that showed inverse expression in PCA were obtained to establish a regulatory network. In this regulatory network, 10 genes (BCL2, BNC2, CCND2, EPM2A, MRAS, NAV2, RASL12, STK33, TCEAL1, WWC2) were co-regulated by 5 miRNAs (hsa-miR-106b, hsa-miR-130b, hsa-miR-93, hsa-miR-153, hsa-miR-182). The expression of hsa-miR-182 was significantly associated with PCA survival through the online validation tool of SurvMicro, suggesting the potential use as a diagnostic or prognostic biomarker in PCA.

Conclusion

This integrated analysis was performed to infer new miRNA regulation activities, which provides insights into the understanding of underlying molecular mechanisms of PCA, and guides for exploration of novel therapeutic targets.

Section snippets

Gene Expression Profiles

We searched the Gene Expression Omnibus database (GEO, http://www.ncbi.nlm.nih.gov/geo) for miRNA and gene expression datasets. GEO served as a public repository for gene expression datasets, initiated by the growing demand for a public repository for high-throughput gene expression data.⁸ We only retained datasets that analyzed both miRNA and gene expression profiling of PCA in 1 study to minimize the heterogeneity.

Differential Analysis of miRNA and Genes

Due to the heterogeneity of multiple microarray datasets caused by different

Differentially Expressed miRNAs and Genes in the PCA

In this work, we collected a total of 3 microarray studies, and it contains 197 samples of PCA and 43 samples of normal control, respectively (Supplementary Table S1). After normalization of the original miRNA and gene expression data, we performed differential expressed analysis between PCA and normal control samples using MATLAB. Finally, 29 miRNAs were regarded as significantly differentially expressed miRNA under the threshold of P value < .01 and effect size > 0.8, with 10 upregulated and

Discussion

It has been widely accepted that oncogenesis and tumor progression is initiated through a deregulated expression of oncogenes and tumor suppressor genes that further triggers the malignant transformation of the affected cells. miRNAs, as posttranscriptional regulators of around 30% of the human genome, are becoming more and more necessary to understand the mechanisms leading to cancer. Widespread deregulation of miRNA expression occurs in human PCA. In this study, after combining with miRNA and

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: Yanan Sun and Xiaopeng Jia contributed equally to this study and thus share first authorship.

: Financial Disclosure: The authors declare that they have no relevant financial interests.

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Basic and Translational ScienceScreening of Differently Expressed miRNA and mRNA in Prostate Cancer by Integrated Analysis of Transcription Data

Objective

Materials and Methods

Results

Conclusion

Section snippets

Gene Expression Profiles

Differential Analysis of miRNA and Genes

Differentially Expressed miRNAs and Genes in the PCA

Discussion

J Biomed Inform

Blood

J Biol Chem

J Urol

MicroRNA biogenesis and cancer

Methods Mol Biol

A microRNA expression signature of human solid tumors defines cancer gene targets

Proc Natl Acad Sci USA

MicroRNA expression profiles classify human cancers

Nature

MicroRNA expression profiling in prostate cancer

Cancer Res

Genomic profiling of microRNA and messenger RNA reveals deregulated microRNA expression in prostate cancer

Cancer Res

Widespread deregulation of microRNA expression in human prostate cancer

Oncogene

MicroRNA145 targets BNIP3 and suppresses prostate cancer progression

Cancer Res

Gene Expression Omnibus: NCBI gene expression and hybridization array data repository

Nucleic Acids Res

An in silico analysis of dynamic changes in microRNA expression profiles in stepwise development of nasopharyngeal carcinoma

BMC Med Genomics

miRNA-mRNA integrated analysis reveals roles for miRNAs in primary breast tumors

PLoS ONE

PathwayVoyager: pathway mapping using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database

BMC Genomics

Basic and Translational Science
Screening of Differently Expressed miRNA and mRNA in Prostate Cancer by Integrated Analysis of Transcription Data