Describing the predictory role of hMOB2 in cancer treatment

Cancer is defined as the continuous proliferation of cells due to the dysfunction of proteins resulting from mutations in genes involved in cell growth, division, differentiation and programmed cell death. The increasing number of cancer cases and cancer-related death rates each year highlight the importance of cancer treatments. In studies focused on personalised cancer treatment, it is crucial to identify the functions of proteins in the DNA damage response system and to understand the functions of cell cycle and metabolism. In this thesis, the molecular mechanism of hMOB2 using osteosarcoma U2OS cells and the predictive role of hMOB2 in individualised cancer therapies using MCF-7 cell line were investigated. The synthetic lethal interactions of the hMOB2 protein with components involved in various cellular pathways were identified using RT-PCR. The subcellular localisation and post-translational modification status of hMOB2 protein in response to DNA damage were determined through co-localizations with RAD51, ATM, 53BP1, and H2AX proteins using immunofluorescence techniques. The crystal violet cell viability, colony survival, Western blot, wound healing, DNA fragmentation and neutral red analyses of MCF-7 cells treated with PARP inhibitors olaparib, rucaparib and veliparib were performed. The findings of our study showed that the hMOB2 protein is likely to have potential synthetic lethal interactions with various celular components and co-localises with 53BP1 and H2AX proteins in response to DNA damage. In hMOB2 defective MCF-7 breast cancer cells, PARP inhibitor treatments were found to reduce cell viability, suppress colony survival, inhibit cell migration, and regulate the expression levels of apoptosis-related proteins, leading to DNA damage and apoptosis.