Abstract
Purpose: Aberrant expression of microRNAs (miRNAs) has been discovered in prostate cancer progression however their function is not well understood, thereby further investigation is required to understand the importance of underlying mechanisms and their involvement in multiple signaling pathways, as well as their potential as therapeutic targets. In this study the role and expression levels of three miRNAs were evaluated: miR-21, miR-221 and miR-200c in different prostate cancer cell lines. In addition, based on the latest studies on miRNAs function, their association with other target genes and molecules were analyzed using bioinformatic tools. Methods: Three PCa cell lines PC3, LNCaP and VCaP and normal prostate epithelial cell line PNT1A were screened for miRNA expression levels using qPCR. miRNA target genes and their association with signaling pathways were analyzed through several Network and pathway analysis online tools. Findings: Upregulation of miR-21 and miR-221 was observed in PC3 and VCaP prostate cancer cells, respectively. According to KEGG analysis, we found that Hippo signaling pathway and cytokine-cytokine receptor interactions were affected by miR-21 while miR-221 would interfere with ECM-receptor interaction, Fatty acid elongation and Huntington disease molecular networks. Exposure of PC3 cells to TGF-β (10 µM) caused upregulation of miR-21 with the evidence with increased invasion potential. Discussion and Conclusion: miRNAs could regulate several genes in multiple signaling pathways. Here, we demonstrated that in a panel of PCa cell lines, both mir-21 and miR-221 expressions were upregulated. miR-21 may be a dignostic and prognosticbiomarker for PCa.
Highlights
Prostate cancer (PCa) is the most common cancer in men and a major cause of cancer-related deaths worldwide [1] PCa often progresses from hormone sensitive to castrate resistance [2]
According to Kyoto encyclopedia of genes and genomes (KEGG) analysis, we found that Hippo signalling pathway and cytokinecytokine receptor interactions were affected by miR-21 while miR-221 would interfere with extracellular matrix (ECM)-receptor interaction, Fatty acid elongation and Huntington disease molecular networks
Gene Ontology (GO) analysis showed that only organelle functions could be a similar target for miR-21 and miR221
Summary
Prostate cancer (PCa) is the most common cancer in men and a major cause of cancer-related deaths worldwide [1] PCa often progresses from hormone sensitive to castrate resistance [2]. Epithelial-mesenchymal transition (EMT), a process that changes epithelial cells into fibroblast looking cell types known as mesenchymal cells, known to play an important role in morphological changes during embryonic development [11] This is highly regulated process is identified to play a role in tumour metastasis; thereby EMT markers could be potential targets for cancer diagnosis and prognosis. E-cadherin, an epithelial marker from a family of cell adhesion molecules (CAMs) is one of the most important molecules encoded by CDH1 gene It plays an important role as a tumour suppressor and found to be suppressed in many cancers such as PCa suggesting that it can be an important marker in cancer progression and metastasis [12]
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