Abstract
Introduction: The microRNA hsa-miR-143-3p (miR-143) has been linked with prostate cancer (PCa) where it is suggested to have a tumour suppressor role. Evidence from other cancers suggests miR-143 acts as an inhibitor of epithelial-mesenchymal transition (EMT), a key biological process required for metastasis. However, in PCa the interaction between miR-143 and EMT-associated mechanisms remains unclear. This project aims to investigate the link between miR-143 and EMT in PCa through in silico and in vitro analyses.
Methods: Expression of miR-143 in The Cancer Genome Atlas Prostate Adenocarcinoma (TCGA-PRAD) repository data was interrogated using CancerMIRNome and UCSC Xena tools. Functional enrichment and network analysis of miR-143 was performed using DAVID and OncomiR tools. Target genes were identified with miRTarBase and miRTargetLink. Expression of miR-143 and selected targets was investigated in vitro by PCR on PCa cell-lines.
Results: TCGA-PRAD dataset analysis showed significant downregulation of miR-143 expression in tumour samples compared to normal samples (p<0.001). Significantly lower levels of miR-143 was also associated with clinicopathological markers of PCa progression (p<0.05). Functional enrichment analysis revealed miR-143 is significantly associated with both PCa and EMT related functions (p<0.05). miR-143 also demonstrates diagnostic value in PCa (AUC=0.89) and lower expression was also associated with poorer patient outcome. Candidate target genes, including ERBB3, MMP9, MYO6 and AKT1, were identified as having a significant inverse correlation with miR-143 in TCGA PRAD data. The link between miR-143 and these targets was validated in cell-lines by PCR.
Conclusion: These results suggest that miR-143 plays an important role in PCa biology and warrants further investigation in this setting. We propose it is linked to EMT and has potential clinical utility as a biomarker for PCa. However, more research is required to further validate the impact of miR-143 upon target genes and elucidate its exact role in EMT.
Methods: Expression of miR-143 in The Cancer Genome Atlas Prostate Adenocarcinoma (TCGA-PRAD) repository data was interrogated using CancerMIRNome and UCSC Xena tools. Functional enrichment and network analysis of miR-143 was performed using DAVID and OncomiR tools. Target genes were identified with miRTarBase and miRTargetLink. Expression of miR-143 and selected targets was investigated in vitro by PCR on PCa cell-lines.
Results: TCGA-PRAD dataset analysis showed significant downregulation of miR-143 expression in tumour samples compared to normal samples (p<0.001). Significantly lower levels of miR-143 was also associated with clinicopathological markers of PCa progression (p<0.05). Functional enrichment analysis revealed miR-143 is significantly associated with both PCa and EMT related functions (p<0.05). miR-143 also demonstrates diagnostic value in PCa (AUC=0.89) and lower expression was also associated with poorer patient outcome. Candidate target genes, including ERBB3, MMP9, MYO6 and AKT1, were identified as having a significant inverse correlation with miR-143 in TCGA PRAD data. The link between miR-143 and these targets was validated in cell-lines by PCR.
Conclusion: These results suggest that miR-143 plays an important role in PCa biology and warrants further investigation in this setting. We propose it is linked to EMT and has potential clinical utility as a biomarker for PCa. However, more research is required to further validate the impact of miR-143 upon target genes and elucidate its exact role in EMT.
Original language | English |
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Publication status | Unpublished - 2023 |
Event | Irish Association of Cancer Research Annual Conference 2023 - Athlone, Ireland Duration: 22 Feb 2023 → 24 Feb 2023 https://www.iacr.ie/2023-conference-information/ |
Conference
Conference | Irish Association of Cancer Research Annual Conference 2023 |
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Country/Territory | Ireland |
Period | 22/02/23 → 24/02/23 |
Internet address |