Identification of miRNAs that are involved in the regulation of tumor suppressor MTUS1 gene and potential use of these miRNAs in cancer therapy

Microtubule-Associated Tumor Suppressor 1 (MTUS1) is a candidate tumor suppressor gene which is associated with cell proliferation and apoptosis. Major protein isoform encoded by this gene is ATIP3. MTUS1/ATIP3 was shown to be downregulated in various types of cancers and reduced MTUS1/ATIP3 expression was associated with increased proliferation and migration of cancer cells. Also, MTUS1/ATIP3 was reported to be overexpressed in some types of cancers such as prostate and esophageal cancer. Accordingly, the role of MTUS1/ATIP3 in the formation of cancer was not fully elucidated. In this study, we aimed to determine the role of MTUS1/ATIP3 in lung, breast and osteosarcoma cancers and miRNAs involved in the regulation of MTUS1 gene. Firstly, expressions levels of ATIP3 and total MTUS1 comprising all slice variants were determined in lung (A549), breast (MCF-7) and osteosarcoma (U2OS) cancer and control cell lines. Also, in order to determine the effect of MTUS1/ATIP3 on cell proliferation, migration, colony formation and apoptosis, ATIP3 was overexpressed in cancerous cell lines. Also, miRNA mimic experiments were performed to demonstrate the role of let-7b-5p, let-7c-5p, miR-96-5p and miR-125b-5p miRNAs in the regulation of MTUS1. Consequently, while the expression levels of ATIP3 and total MTUS1 were significantly reduced in breast cancer, they were significantly increased in lung and osteosarcoma cells as compared to controls. After ATIP3 overexpression, there was no significant difference in cell proliferation, migration, colony formation capacity and apoptosis induction. Additionally, after mimic transfections miRNAs were overexpressed but this expression increments had no statistically significant effect on ATIP3 and total MTUS1 expression levels. In conclusion, our findings suggest that MTUS1/ATIP3 does not have tumor suppressor activities in lung, breast and osteosarcoma cancers and the studied miRNAs are not involved in MTUS1/ATIP3 regulation.