The role of TRIM36 in breast cancer

Breast cancer is the most commonly diagnosed cancer and the second leading cause of cancer-related deaths worldwide. Elucidating the protein complexes within signaling pathways involved in the initiation and progression of breast cancer may facilitate the identification of novel therapeutic targets. Recent studies have highlighted the role of TRIM36 in cancers such as prostate and lung; however, its association with breast cancer remains unexplored. In this study, we investigated the relationship between TRIM36 expression levels and breast cancer pathogenesis. Additionally, TRIM36 expression was silenced and/or rapamycin was administered in breast cancer cell lines MCF-7 and MDA-MB-231 to evaluate its effects on cell migration and proliferation using wound healing and colony formation assays. To this end, the relative TRIM36 mRNA expression levels were quantified by quantitative real time PCR in normal and tumor tissues collected from 45 breast cancer patients. TRIM36 expression was confirmed in breast tissue, but no statistically significant difference was observed in TRIM36 mRNA expression levels between normal and tumor tissues. Immunoblotting analysis in breast cancer cell lines revealed higher TRIM36 expression levels in MCF-7 cells, which are less aggressive compared to MDA-MB-231 cells. TRIM36 silencing was achieved in both cell lines via siRNA transfection, as confirmed by immunoblotting. Following transfection, wound healing and colony formation assays were conducted. Results indicated that TRIM36 silencing in MCF-7 cells enhanced cell migration, supporting its potential tumor suppressor role. In addition to transfection experiments, rapamycin, an mTOR inhibitor, was administered to transfected and non-transfected cells at IC50 concentrations specific to each cell type. Subsequent wound healing and colony formation assays demonstrated that rapamycin treatment alone increased TRIM36 expression levels in both cell lines, as verified by immunoblotting. In wound healing assays, combined treatment with rapamycin and TRIM36 silencing showed greater inhibition of cell migration in MCF-7 cells, whereas rapamycin alone was more effective in MDA-MB-231 cells. Colony formation assays revealed that TRIM36 silencing in MCF-7 cells and combined treatment in MDA-MB-231 cells led to a significant reduction in colony numbers compared to other treatments. This study uniquely contributes to the understanding of TRIM36's role in breast cancer biology and provides a new perspective from which TRIM36 silencing and/or rapamycin administration can be considered as an individualized therapeutic strategy. These findings position TRIM36 as a promising target molecule for future molecular cancer research and therapeutic development.