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

Abstract

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.

The Pervasive Role of the miR-181 Family in Development, Neurodegeneration, and Cancer

“…The oncogenic activity of miR-181a has been functionally linked to the suppression of the Smad repressor TGIF2 and to the promotion of the EMT process in PCa cells [53]. More recently, according to the hypothesis that miR-181a acts as oncomiR, it has been shown that miR-181a is up-regulated in advanced stages of prostate cancer and it is involved in drug resistance [81].…”

Autophagy-mediated reduction of miR-345 contributes to hepatic cystogenesis in polycystic liver disease

“…9,20 Our data are in line with other reports showing altered miRNA profiles in multiple pathological conditions with the majority of miRNAs being decreased. [21][22][23][24] Combined miRNA-seq -mRNA-seq analysis for targets of down-regulated miRNAs in PLDC identified the cell cycle, autophagy, cAMP-mediated signaling and cell proliferation as four most affected pathways. All of these pathways play a critical role in J o u r n a l P r e -p r o o f hepatic cystogenesis and have been considered for therapeutic interventions in PLD.…”

What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 5: Epigenetic Regulation of PD-L1

“…PDGF (involved in EMT) and other growth factors regulate miR-200 expression, while miR-200c directly influences the EGFR and TGF-β receptor signaling [202][203][204]. miR-200b seems significantly downregulated in castration-resistant PCs: miR-200 influences Notch1 expression, and together they regulate EMT progression [205]. miR-200c expression is negatively regulated by ERG in PC cells lines [206].…”