Identification of Key MicroRNAs and Mechanisms in Prostate Cancer Evolution Based on Biomarker Prioritization Model and Carcinogenic Survey
| Autor: | Yuhua Huang, Jianquan Hou, Yuxin Lin, Xuefeng Zhang, Xuedong Wei, Bairong Shen, Zhijun Miao |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
lcsh:QH426-470 Systems biology Computational biology Biology 03 medical and health sciences Prostate cancer 0302 clinical medicine prostate cancer management Prostate microRNA medicine Genetics Translational research informatics Genetics (clinical) Original Research miRNA regulatory pattern Wnt signaling pathway Cancer systems biology medicine.disease body regions lcsh:Genetics 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis embryonic structures Molecular Medicine Biomarker (medicine) miRNA biomarker miRNA-mRNA network modeling |
| Zdroj: | Frontiers in Genetics Frontiers in Genetics, Vol 11 (2021) |
| ISSN: | 1664-8021 |
| Popis: | Background: Prostate cancer (PCa) is occurred with increasing incidence and heterogeneous pathogenesis. Although clinical strategies are accumulated for PCa prevention, there is still a lack of sensitive biomarkers for the holistic management in PCa occurrence and progression. Based on systems biology and artificial intelligence, translational informatics provides new perspectives for PCa biomarker prioritization and carcinogenic survey.Methods: In this study, gene expression and miRNA-mRNA association data were integrated to construct conditional networks specific to PCa occurrence and progression, respectively. Based on network modeling, hub miRNAs with significantly strong single-line regulatory power were topologically identified and those shared by the condition-specific network systems were chosen as candidate biomarkers for computational validation and functional enrichment analysis.Results: Nine miRNAs, i.e., hsa-miR-1-3p, hsa-miR-125b-5p, hsa-miR-145-5p, hsa-miR-182-5p, hsa-miR-198, hsa-miR-22-3p, hsa-miR-24-3p, hsa-miR-34a-5p, and hsa-miR-499a-5p, were prioritized as key players for PCa management. Most of these miRNAs achieved high AUC values (AUC > 0.70) in differentiating different prostate samples. Among them, seven of the miRNAs have been previously reported as PCa biomarkers, which indicated the performance of the proposed model. The remaining hsa-miR-22-3p and hsa-miR-499a-5p could serve as novel candidates for PCa predicting and monitoring. In particular, key miRNA-mRNA regulations were extracted for pathogenetic understanding. Here hsa-miR-145-5p was selected as the case and hsa-miR-145-5p/NDRG2/AR and hsa-miR-145-5p/KLF5/AR axis were found to be putative mechanisms during PCa evolution. In addition, Wnt signaling, prostate cancer, microRNAs in cancer etc. were significantly enriched by the identified miRNAs-mRNAs, demonstrating the functional role of the identified miRNAs in PCa genesis.Conclusion: Biomarker miRNAs together with the associated miRNA-mRNA relations were computationally identified and analyzed for PCa management and carcinogenic deciphering. Further experimental and clinical validations using low-throughput techniques and human samples are expected for future translational studies. |
| Databáze: | OpenAIRE |
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