Background: Src family kinases (SFKs) are pleiotropic activators, proto-oncogenes, mediating extracellular interactions driven by various molecules including the EGFR and integrins. Fyn, a member of the SFKs, was recognized as an important mediator of mitogenic signals and as a regulator of proliferation, adhesion and motility.
MicroRNAs (miRNA) constitute a class of small noncoding RNAs that function as posttranscriptional gene regulators. miRNAs are negative regulators of gene expression, capable of exerting pronounced influences upon the translation and stability of mRNAs. Mounting evidence indicate that aberrantly expressed miRNAs are involved in cancer pathogenesis of solid tumors by their ability to control the expression of protein-coding tumor suppressors and oncogenes.
In a former study, we have established the reciprocal interaction between miR-125a-3p and Fyn in human embryonic cell-line (HEK) and characterized downstream effectors in this cascade, which served as a prototype to further investigate the potential role of miR-125a-3p and its targets in the pathogenesis of prostate cancer.
Results: Overexpression of miR-125a-3p reduced significantly the expression of Fyn mRNAand protein in PC3 cells and led to impaired cell viability and to an arrest at the G2/M phase of the cell cycle. Moreover, overexpressing of miR-125a-3p reduced the activity of FAK, Akt and paxillin and the secretion of VEGF to the culture media. In miR-125a-3p-overexpressing PC3 cells migration was compromised by 50%. Confocal microscopy- live imaging showed a significant decrease in the track speed and track displacement of miR-125a-3p over-expressing cells. The cell viability decreased by 50%. We observed an inverse correlation between the expression of miR-125a and the gleason score in tissue samples obtained from patients diagnosed with prostate cancer.
Conclusions:Our study indicates miR-125a-3p signature in cellular pathways accounted for cell viability and migration of prostate cancer cells. miR-125a-3pmay represent a new plausible therapeutic target in prostate cancer.
