MicroRNA-6833-3p drives prostate cancer progression and stemness by targeting the NUMB-mediated NOTCH signaling pathway.

Abstract

Understanding molecular pathways in prostate cancer (PCa) is essential. This study demonstrates that miR-6833-3p plays a key role in prostate tumorigenesis via multi-omics integration and functional validation. Expression levels of miR-6833-3p, NUMB, and NOTCH1 were measured in PCa cell lines. The direct regulation of NUMB by miR-6833-3p was confirmed via dual-luciferase reporter assays with mutagenesis. Functional effects were examined using NUMB plasmids or miR-6833-3p mimics. Cell function assays and xenograft models in nude mice were employed, with tissues analyzed via HE staining, qRT-PCR, and Western blot. miR-6833-3p and NOTCH1 were upregulated in PCa, while NUMB was downregulated. miR-6833-3p mimics promoted proliferation, migration, and stemness but inhibited apoptosis and the NUMB/NOTCH1 pathway. NUMB overexpression reversed these effects. In vivo, miR-6833-3p accelerated tumor growth and suppressed NUMB/NOTCH1. miR-6833-3p promotes PCa progression and stemness by inhibiting the NUMB-NOTCH pathway, highlighting its potential as a biomarker for detection and targeted therapy.