Non-Coding RNA (Jan 2022)

Hsa-miR-183-5p Modulates Cell Adhesion by Repression of <i>ITGB1</i> Expression in Prostate Cancer

  • Carolina Oliveira-Rizzo,
  • María Carolina Ottati,
  • Rafael Sebastián Fort,
  • Santiago Chavez,
  • Juan Manuel Trinidad,
  • Andrés DiPaolo,
  • Beatriz Garat,
  • José Roberto Sotelo-Silveira,
  • María Ana Duhagon

DOI
https://doi.org/10.3390/ncrna8010011
Journal volume & issue
Vol. 8, no. 1
p. 11

Abstract

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Prostate cancer is a major health problem worldwide. MiR-183 is an oncomiR and a candidate biomarker in prostate cancer, affecting various pathways responsible for disease initiation and progression. We sought to discover the most relevant processes controlled by miR-183 through an unbiased transcriptomic approach using prostate cell lines and patient tissues to identify miR-183 responsive genes and pathways. Gain of function experiments, reporter gene assays, and transcript and protein measurements were conducted to validate predicted functional effects and protein mediators. A total of 135 candidate miR-183 target genes overrepresenting cell adhesion terms were inferred from the integrated transcriptomic analysis. Cell attachment, spreading assays and focal adhesion quantification of miR-183-overexpressing cells confirmed the predicted reduction in cell adhesion. ITGB1 was validated as a major target of repression by miR-183 as well as a mediator of cell adhesion in response to miR-183. The reporter gene assay and PAR-CLIP read mapping suggest that ITGB1 may be a direct target of miR-183. The negative correlation between miR-183 and ITGB1 expression in prostate cancer cohorts supports their interaction in the clinical set. Overall, cell adhesion was uncovered as a major pathway controlled by miR-183 in prostate cancer, and ITGB1 was identified as a relevant mediator of this effect.

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