Identifying the key genes and microRNAs in prostate cancer bone metastasis by bioinformatics analysis.

Zhiguo Zhu,Yihan Deng,Yaoan Wen,Qian Xiang,Shankun Zhao,Chunxiang Xuan,Zhigang Zhao,Jiamin Wang,Qingping Chen,Yangzhou Liu,Lianmin Luo

doi:10.1002/2211-5463.12805

Abstract

Prostate adenocarcinoma (PCa) is the most common cause of death due to malignancy among men, and bone metastasis is the leading cause of mortality in patients with PCa. Therefore, identifying the causes and molecular mechanism of bone metastasis is important for early detection, diagnosis and personalized therapy. In this study, we systematically analyzed molecular correlates of bone metastasis by bioinformatics analysis. A total of 12 differentially expressed microRNAs (miRNAs) and 102 differentially expressed genes were identified. Five miRNAs had prognostic significance in biochemical recurrence‐free survival (miR‐636, miR‐491‐5p, miR‐199b‐5p, miR‐199b‐3p, miR‐28‐3p). The differentially expressed genes were significantly enriched in extracellular matrix, cell‐substrate adhesion, collagen and integrin. Seven hub genes (VCAN, COL3A1, COL1A1, APOE, COL1A2, SDC1, THY1) with worse biochemical recurrence‐free survival and one hub gene (MMP9) with worse overall survival were detected. miR‐636, a novel oncogene, was found to be up‐regulated in bone metastatic PCa tissues and also predominately up‐regulated in human PCa cell lines. miR‐636 promoted cellular invasion and migration, and may promote bone metastasis via targeting MBNL2, TNS1 and STAB1. In conclusion, we have successfully defined molecular signatures of bone metastasis in PCa.

Highlights

Prostate adenocarcinoma (PCa) is the most common cause of death due to malignancy among men, and bone metastasis is the leading cause of mortality in patients with PCa
We performed pathway and process enrichment analysis of differentially expressed gene (DEG), built a protein–protein interaction (PPI) network to describe the relationship of DEGs and performed Hub gene and Module analysis
muscleblind-like splicing regulator 2 (MBNL2), tensin 1 (TNS1) and special AT-rich sequence binding protein 1 (STAB1) may be the targets of miR-636 to promote bone metastasis

Summary

Materials and methods

LIMMA, an R package for the analysis of gene expression microarray data, was used to extract differentially expressed miRNAs (DE-miRNAs) and differentially expressed genes (DEGs) [12]. G. Zhao (Unpublished data) aSequencing by Illumina HiSeq 2500 (Illumina Inc.) platform. Gene Expression Profiling Interactive Analysis (GEPIA; http://gepia.cancer-pku.cn) was used to assess the prognostic significance of target genes of miR-636. RWPE-1 was grown in keratinocyte serum-free medium (Gibco, Shanghai, China) supplemented with 0.05 mgÁmLÀ1 bovine pituitary extract and 5 ngÁmLÀ1 human recombinant epidermal growth factor. A GraphPad SoftwareP-value < 0.05 indicated statistical significance

Results

Discussion

Conflict of interest