Dataset Information

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

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.

SUBMITTER: Zhu Z

PROVIDER: S-EPMC7137804 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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

Zhu Zhiguo Z Wen Yaoan Y Xuan Chunxiang C Chen Qingping Q Xiang Qian Q Wang Jiamin J Liu Yangzhou Y Luo Lianmin L Zhao Shankun S Deng Yihan Y Zhao Zhigang Z

FEBS open bio 20200319 4

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 differen ...[more]

PMID: 32027093

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Project description:BackgroundMetastatic prostate cancer (PCa) is a lethal tumor. However, the molecular mechanisms underlying PCa progression have not been fully elucidated.MethodsTranscriptome expression profiling and clinical information on primary and metastatic PCa samples were obtained from TCGA. R software was used to screen the DEGs, and LASSO logistical regression method was utilized to identify the pivotal PCa metastasis-related DEGs. The transcriptional expression levels of the key genes were analyzed using the UALCAN database, and the corresponding protein expression were validated by Immunohistochemistry (IHC). Survival analysis of the key genes was performed using the GEPIA database. Wound healing assay and Transwell assay were conducted to determine whether knockdown of the key genes influence the migration and invasion abilities of PCa cells (22Rv1 and PC3). GSEA was performed to predict key genes-mediated signaling pathways for the development of PCa. Western blotting was used to evaluate the expression changes of E-cadherin, Twist1, and Vimentin in PCa cells with the key genes silencing. An in vivo mouse metastatic model for PCa was also generated to verify the important role of ISG15 and CST2 in PCa metastasis.ResultsA comparison between primary and metastatic PCa tissues was conducted, and 19 DEGs were screened. Among these, three key genes were identified that might be closely associated with PCa progression according to the LASSO logistical analysis, namely ISG15, DNAH8, and CST2. Further functional experiments revealed that knockdown of ISG15 and CST2 suppressed wound healing, migration, and invasion of PCa cells. To explore the molecular mechanism of ISG15 and CST2 in the development of PCa, GSEA was performed, and it was found that both genes play crucial roles in cell adhesion molecules, extracellular matrix-receptor interaction, and focal adhesion. Western blotting results exhibited that inhibiting ISG15 and CST2 led to increase the expression of E-cadherin and decrease the expression of Twist1 and Vimentin. Additionally, the metastatic in vivo study demonstrated that both PC3 and 22Rv1 cells expressing with luciferase-shISG15 and luciferase-shCST2 had significantly lower detectable bioluminescence than that in the control PCa cells.ConclusionISG15 and CST2 may participate in PCa metastasis by regulating the epithelial-mesenchymal transition (EMT) signaling pathway. These findings may help to better understand the pathogenetic mechanisms governing PCa and provide promising therapeutic targets for metastatic PCa therapy.

Project description:Wilms tumor (WT) is one of the most common types of pediatric solid tumors; however, its molecular mechanisms remain unclear. The present study aimed to identify key genes and microRNAs (miRNAs), and to predict the underlying molecular mechanisms of WT using integrated bioinformatics analysis. Original gene expression profiles were downloaded from the Gene Expression Omnibus (GEO; accession, GSE66405) and The Cancer Genome Atlas (TCGA) databases. Similarly, miRNA expression patterns were downloaded from GEO (accession, GSE57370) and TCGA. R version 3.5.0 software was used to identify differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs) using the limma and edgeR packages. Kyoto Encyclopedia of Genes and Genomes pathway and Gene Ontology analyses were performed to examine the biological functions of the DEGs. Additionally, a protein-protein interaction (PPI) network was constructed to screen hub gene modules using Cytoscape software. By predicting target genes of the DEMs and integrating them with DEGs, the present study constructed a miRNA-mRNA regulatory network to predict the possible molecular mechanism of WT. Expression of hub genes was validated using the Oncomine database. A total of 613 genes and 29 miRNAs were identified to be differentially expressed in WT. By constructing a PPI network and screening hub gene modules, 5 upregulated genes, including BUB1 mitotic checkpoint serine/threonine kinase, BUB1B mitotic checkpoint serine/threonine kinase B, cell division cycle protein 45, cyclin B2 and pituitary tumor-transforming 1. These genes were identified to be associated with the cell cycle pathway, which suggested that these genes may serve important roles in WT. In addition, a miRNA-mRNA regulatory network was constructed and comprised 16 DEMs and 19 DEGs. In conclusion, key genes, miRNAs and the mRNA-miRNA regulatory network identified in the present study may improve understanding of the underlying molecular mechanisms in the occurrence and development of WT, and may aid the identification of potential biomarkers and therapeutic targets.

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

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

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