In silico analysis of prognostic and diagnostic significance of target genes from prostate cancer cell lines derived exomicroRNAs

Antonio Altuna-Coy; Xavier Ruiz-Plazas; Verónica Arreaza-Gil; José Segarra-Tomás; Matilde R Chacón

doi:10.1186/s12935-023-03123-1

In silico analysis of prognostic and diagnostic significance of target genes from prostate cancer cell lines derived exomicroRNAs

Cancer Cell Int. 2023 Nov 17;23(1):275. doi: 10.1186/s12935-023-03123-1.

Authors

Antonio Altuna-Coy^#¹, Xavier Ruiz-Plazas^#^{1

2}, Verónica Arreaza-Gil¹, José Segarra-Tomás^#^{1

2}, Matilde R Chacón^#³

Affiliations

¹ Disease Biomarkers and Molecular Mechanisms Group, IISPV, Joan XXIII University Hospital, Universitat Rovira I Virgili, C/Dr. Mallafré Guasch, 4,, 43007, Tarragona, Spain.
² Urology Unit, Joan XXIII University Hospital, Tarragona, Spain.
³ Disease Biomarkers and Molecular Mechanisms Group, IISPV, Joan XXIII University Hospital, Universitat Rovira I Virgili, C/Dr. Mallafré Guasch, 4,, 43007, Tarragona, Spain. mrch2424@gmail.com.

^# Contributed equally.

Abstract

Background: Cancer-secreted exovesicles are important for cell-to-cell communication by altering cancer-related signalling pathways. Exovesicles-derived miRNAs (exomiRNAs)-target genes can be useful for diagnostic and prognostic purposes.

Methods: ExomiRNA from prostate cancer (PCa) cells (PC-3 and LNCaP) were quantified by qRT-PCR and compared to the healthy cell line RWPE-1 by using miRNome PCR 752 miRNAs Panel. MiRNet database was used to predict exomiRNA-target genes. ExomiRNA-target genes pathway functional enrichment was performed by using Reactome database and Enrichr platform. Protein-protein interaction analysis was carried out by using the STRING database. RNA target-gene sequencing data from The Cancer Genome Atlas Prostate Adenocarcinoma (TCGA-PRAD) database was screened out in 465 PCa patients for candidate gene expression in prostate tumour (PT) tissue and non-pathologic prostate (N-PP) tissue. Signature gene candidates were statistically analysed for diagnosis and prognosis usefulness.

Results: A total of 36 exomiRNAs were found downregulated when comparing PCa cells vs a healthy cell line; and when comparing PC-3 vs LNCaP, 14 miRNAs were found downregulated and 52 upregulated. Reactome pathway database revealed altered pathways and genes related to miRNA biosynthesis, miRNA-mediated gene silencing (TNRC6B and AGO1), and cell proliferation (CDK6), among others. Results showed that TNRC6B gene expression was up-regulated in PT tissue compared to N-PP (n = 52 paired samples) and could be useful for diagnostic purposes. Likewise, gene expression levels of CDK6, TNRC6B, and AGO1 were down-regulated in high-risk PT (n = 293) compared to low-risk PCa tissue counterparts (n = 172). When gene expression levels of CDK6, TNRC6B, and AGO1 were tested as a prognostic panel, the results showed that these improve the prognostic power of classical biomarkers.

Conclusion: ExomiRNAs-targets genes, TNRC6B, CDK6, and AGO1, showed a deregulated expression profile in PCa tissue and could be useful for PCa diagnosis and prognosis.

Keywords: Diagnosis; Exovesicles; Prognosis; Prostate cancer; Targets; exomiRNAs.

Grants and funding

INVESTIGO CONTRACT/Agència de Gestió d'Ajuts Universitaris i de Recerca