| Aims: MicroRNAs (miRs) are key modulators of cellular processes such as proliferation, apoptosis, as well as
anti-cancer immune responses. Here, we evaluated the role of miR-424-5p in breast cancer (BC) and investigated
its effects on T cell-related immune response.
Main methods: BC tissues and cell lines were prepared and the expression of miR-424-5p and PD-L1, as well as
the underlying molecular pathways, were assessed via qRT-PCR and western blotting. The MTT assay and flow
cytometry were used to assess the effect of miR-424-5p on proliferation, apoptosis, autophagy, and cell cycle
progression. The co-culture of T cells with MDA-MB-231 was performed for evaluating the role of miR-424-5p in
rescuing T cell exhaustion.
Key findings: The results indicated the down-regulation of miR-424-5p and up-regulation of PD-L1 expression in
BC tissue specimens. MiR-424-5p transfection into PD-L1 overexpressing MDA-MB-231 cells decreased the expression
of PD-L1. Also, miR-424-5p could reduce MDA-MB-231 cell viability through modulating apoptosis and
autophagy pathways. Furthermore, miR-424-5p transfection leads to decreased colony formation and increased
cell number at the G2/M phase. Western blot analysis illustrated that miR-424-5p could exert its anti-proliferative
effect via modulating PTEN/PI3K/AKT/mTOR pathway. Moreover, it was demonstrated that suppression
of PD-L1 by miR-424-5p could participate in regulating the expression of effector cytokines in T cells.
Significance: MiR-424-5p could be considered as a potential tumor-suppressor miR in regulating BC cellular
growth, apoptosis, and T cell-related immune response through targeting PD-L1, and its downstream mediators.
Therefore, we recognized miR-424-5p as a promising candidate for miR restoration therapy in BC patients. |