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PLoS One. 2019 Nov 22;14(11):e0224071. doi: 10.1371/journal.pone.0224071. eCollection 2019.

Integrated analysis of miRNA landscape and cellular networking pathways in stage-specific prostate cancer.

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Department of Urology, Case Western Reserve University, School of Medicine, Cleveland, OH, United States of America.
The Urology Institute, University Hospitals Cleveland Medical Center, Cleveland, OH, United States of America.
Center of Gene Regulation in Health and Disease, Cleveland State University, Cleveland, OH, United States of America.
Department of Inflammation and Immunity, Cleveland Clinic, Cleveland, OH, United States of America.
Department of Nutrition, Case Western Reserve University, Cleveland, OH, United States of America.
Division of General Medical Sciences, Case Comprehensive Cancer Center, Cleveland, OH, United States of America.
Department of Urology, Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, OH, United States of America.


Dysregulation of miRNAs has been demonstrated in several human malignancies including prostate cancer. Due to tissue limitation and variable disease progression, stage-specific miRNAs changes in prostate cancer is unknown. Using chip-based microarray, we investigated global miRNA expression in human prostate cancer LNCaP, PC3, DU145 and 22Rv1 cells representing early-stage, advanced-stage and castration resistant prostate cancer in comparison with normal prostate epithelial cells. A total of 292 miRNAs were differentially expressed with 125 upregulated and 167 downregulated. These miRNAs were involved in pathways including drug resistance drug-efflux, adipogenesis, epithelial-to-mesenchymal transition, bone metamorphosis, and Th1/Th2 signaling. Regulation of miRNAs were interlinked with upstream regulators such as Argonaut 2 (AGO2), Double-Stranded RNA-Specific Endoribonuclease (DICER1), Sjogren syndrome antigen B (SSB), neurofibromatosis 2 (NF2), and peroxisome proliferator activated receptor alpha (PPARA), activated during stage-specific disease progression. Candidate target genes and pathways dysregulated in stage-specific prostate cancer were identified using CS-miRTar database and confirmed in clinical specimens. Integrative network analysis suggested some genes targeted by miRNAs include miR-17, let7g, miR-146, miR-204, miR-205, miR-221, miR-301 and miR-520 having a major effect on their dysregulation in prostate cancer. MiRNA-microarray analysis further identified miR-130a, miR-181, miR-328, miR146 and miR-200 as a panel of novel miRNAs associated with drug resistance drug-efflux and epithelial-to-mesenchymal transition in prostate cancer. Our findings provide evidence on miRNA dysregulation and its association with key functional components in stage-specific prostate cancer.

Conflict of interest statement

The authors have declared that no competing interests exist.

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