Functional interaction between miR-505-3p and miR-21 contributes to GBM suppression

Recently, studies have shown that non-coding RNAs (ncRNAs) play an important role in cancer. An important group of these ncRNAs are micro RNAs (miRs), which are important regulators in the cell. miR-21 is one type of miR that plays an oncogenic role in various cancers, especially glioblastoma (GBM). On the other hand, according to the studies, miR-505-3p is known as a tumor suppressor (TSG). Other studies conducted in recent years indicate that miRs may target other ncRNAs, including other miRs. This mode is called miR-miR interaction. Therefore, this study aims to investigate the relationship of these two miRs in GBM. Bioinformatic analyses predicted a potential interaction between miR-505-3p and pri-miR-21. RNA hybridization modeling suggested thermodynamically feasible binding. Overexpression of miR-505-3p in GBM cell lines (U87-MG and A172) was associated with reduced levels of mature miR-21-5p. Concomitantly, increased mRNA and protein expression of known miR-21 target genes, including PDCD4, HNRNPK, and RECK, was observed. Functional assays demonstrated reduced cell proliferation and increased sub-G1 cell population following miR-505-3p overexpression. Dual luciferase reporter assays using a pri-miR-21 construct suggested that miR-505-3p may interfere with miR-21 processing. Our findings suggest that miR-505-3p may modulate miR-21 expression and is associated with restoration of tumor suppressor gene expression in GBM cells. While the data support a potential regulatory relationship, the precise molecular mechanism remains to be elucidated. Further studies are required to determine whether miR-505-3p directly interacts with pri-miR-21 and to clarify the biological relevance of this axis in GBM.