Exosome-derived hsa-miR-200c-3p, hsa-miR-25-3p and hsa-miR-301a-3p as potential biomarkers and therapeutic targets for restoration of PTEN expression in clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is an aggressive kidney cancer subtype with limited biomarkers and therapeutic options. Thus, the present study aimed to evaluate the biomarker and therapeutic potential of Phosphatase and Tensin Homologue (PTEN)-regulating microRNAs (miRNAs) in 2D and 3D ccRCC models. Extracellular vesicles (EVs) from four renal cell lines were characterized, and selected miRNAs (hsa-miR-200c-3p, hsa-miR-25-3p, and hsa-miR-301a-3p) were quantified in cells and EVs. PTEN mRNA levels were measured intracellularly. 786-O cells were transfected with miRNA inhibitors in both models and effects on miRNA and PTEN expression were assessed alongside phenotypic alterations. The expression of target miRNAs increased with ccRCC cell aggressiveness, both intracellularly and in EVs, while PTEN mRNA expression decreased. Combined inhibition of these miRNAs significantly increased PTEN expression, reducing tumor cell proliferation and migration in 2D models and decreasing spheroid size and metabolic capacity in 3D models. These miRNAs show potential as biomarkers for monitoring disease aggressiveness and as therapeutic targets in ccRCC, potentially leading to more effective and personalized treatment approaches for ccRCC patients.