Science and Technology Production
Medicina - MiR-19b-3p and miR-101-3p: key prostate cancer oncomiRs with diagnostic and prognostic value
Congreso
Date:
2021Publishing House and Editing Place:
Ethel Di VitaISSN:
1669-9106Summary *
Prostate cancer (PCa) is the most commonly diagnosed male malignancy worldwide and the third cause of death by cancer in Argentinian men. High fat diet (HFD) and metabolic syndrome (MeS) increase PCa risk and aggressiveness. MiRNAs are small non-coding RNA molecules that regulate gene expression and can be secreted by tumor cells into the bloodstream. Our aim was to identify miRNAs-based biomarkers for diagnosis and prognosis of PCa associated with MeS. NSG mice chronically fed with HFD or control diet (CD) were s.c. inoculated with PC3 cell line. After tumor growth, mice were sacrificed, plasma and tumors were collected. PC3 xenograft from HFD-fed mice significantly increased the expression of hsa-miR-19b-3p,-320a-5p,-101-3p,-3613-3p,-1207-5p,-5095 and -2277-5p compared to CD-fed mice. Using DIANA-miRPath v3 and DIANA-TarBase v7 tools we found that these miRNAs modulate specific metabolic and cancer related pathways and more than 1,100 validated targets involved in proteoglycans in cancer and fatty acid biosynthesis. Furthermore, using bioinformatic tools and human datasets we demonstrated that these 2 miRNAs were significantly increased in the bloodstream of PCa patients compared to non-PCa volunteers, in prostate tumors compared to normal adjacent tissues (NAT) and in tumors of metastatic patients compared to tumors of non-metastatic patients. In addition, miR-101-3p was increased in exosomes isolated from blood of PCa patients. Finally, we established that 6 target genes that negatively correlate with miR-19b-3p in prostate tumor samples from patients were involved in Proteoglycan in cancer and Focal adhesion pathways and were down-regulated in tumors compared to NAT. No significant changes in the expression of miR-101-3p target genes were found in tumor compared with NAT. In summary, we propose miR-19b-3p and miR- 101-3p as oncomiRs at tumor and metastatic site level, respectively, that can be useful as prognosis and diagnosis biomarkers. Information provided by the agent in SIGEVAKey Words
PROSTATE CANCERONCOMIRSMIRNAS