Negative Correlation between SMARCAD1 and Histone Citrulline Protein Expression in Cancer and Non-cancerous Cell Lines

Author(s): Zhao, Tianyi | Advisor(s): Zhong, Sheng | Abstract: SMARCAD1 is a matrix-associated actin-dependent regulator of chromatin that encodes SWI/SNF subfamily of helicase proteins. It has been shown that the functions of SMARCAD1 are linked to histone 3 citrullination, a specific type of histone post-translational modifications. Histone citrullination can lead to alterations in protein functions, and affect gene expressions. This peptidylarginine deiminases (PADIs) catalyzed post-translational modification also increases in the progression of cancer. Interestingly, human renal cancer cells exhibit low to non-detection of SMARCAD1 protein expression. It is anticipated that an association between SMARCAD1 and histone 3 citrullination function critically in renal cancer and tumor formation. Western blot was performed on mouse cells fist followed by multiple renal cancer and non-cancer human cell lines, to determine SMARCAD1 and histone 3 citrullination protein expression levels and their potential correlation. Multiple cell treatments were introduced and CRISPR/Cas9 gene editing system was used to create SMARCAD1 gene knocking out condition. A negative correlation was determined between SMARCAD1 and citrullination expression level, with a potential positive feedback loop in between SMARCAD1 and histone 3 citrulline enzyme PADI4 in certain cell lines. Moreover, this negative correlation between two protein levels serves as an indicator of renal cancer existence; decrement of SMARCAD1 protein level holds true in renal cancer cells, in parallel with an increment of the histone 3 citrulline protein expression.