Post-translational modifications hold an important role through the regulation of protein activity, turnover, localization and/or interactions. One evolutionary conserved modification involves the covalent attachment of SUMO to different cellular substrates. Covalent modification by SUMO is reversible by the activity of SUMO-specific proteases (SENPs). SENPs have a dual role in the SUMOylation pathway by: (1) processing newly translated SUMO to its active form (hydrolase activity), (2) removing SUMO from substrates (isopeptidase activity). The expression of several SENPs is altered in multiple cancers. De-regulation of either SUMO conjugation or de-conjugation can contribute to cancer progression. SENP5 is a SUMO-specific protease, which displays both hydrolase and isopeptidase activities. Not much is known about SENP5 involvement in cancer development and progression. It has been shown that knockdown of SENP5 in HeLa cells led to a reduction in the proliferation rate. In our research, Kaplan-Meier survival analysis was done on all gene expression measurements in three Breast Cancer datasets, through clinical data to determine a gene’s survival stratification power. SENP5 was the only gene that significantly stratified patients into two survival groups across all three datasets. High expression levels of SENP5 affiliate with low survival, and vice versa. Following these results, we hypothesize that SENP5 has an important role in regulation of breast cancer survival. We tracked phenotypic changes associated with altered SENP5 gene expression, in breast cancer cell-lines as means of identifying the specific mechanism through which SENP5 regulates breast cancer survival. A specific siRNA to SENP5 gene was designed, and its specificity and activity tested by transfection to breast cancer lines. We tested the phenotypic effect of SENP5 silencing on breast cancer lines. Some of the cell-lines showed decreased proliferation, invasiveness and cellular migration following silencing of SENP5. Therefore there must be a mechanism Influenced by SENP5 which affecting breast cancer progression.
