MicroRNA-15a-5p suppresses triple-negative breast cancer cell proliferation and invasion by modulating T-cell immunoreceptor associated with immunoglobulin and ITIM domain expression.

OBJECTIVE: Treating triple-negative breast cancer (TNBC) is a major challenge owing to its unique biological characteristics. This study aimed to elucidate the molecular interaction between microRNA-15a-5p and T-cell immunoreceptor associated with immunoglobulin and ITIM domains (TIGIT) in TNBC.

MATERIAL AND METHODS: The GSE22513 microarray dataset was subjected to bioinformatic analysis. MDA-MB-231 and MDA-MB-468 cells were transfected with lentiviral constructs for overexpressing TIGIT and microRNA (miRNA) mimics for overexpressing miR-15a-5p. Western blot and quantitative real-time polymerase chain reaction analyses were conducted to quantify TIGIT and miR-15a-5p levels of pre- and post-transfection. Cell proliferation, migration, invasiveness, cell cycle distribution, and apoptosis were assessed using cell counting kit-8, wound-healing, colony formation, transwell assays, and flow cytometry, respectively.

RESULTS: This study identified 139 genes (37 upregulated and 102 downregulated genes). Elevated TIGIT levels exhibited a significant link to unfavorable outcomes in individuals with breast cancer (BC). Additional analyses demonstrated that TIGIT expression in BC cell lines was substantially increased compared with that in normal breast cells. Overexpressing miR-15a-5p effectively inhibited TIGIT expression and consequently suppressed TNBC cell proliferation, invasion, and migration. This inhibition prompted G2/M phase accumulation and enhanced cellular mortality.

CONCLUSION: miR-15a-5p exerts tumor-suppressive effects through TIGIT downregulation, thereby mitigating the malignant phenotype of TNBC.