Abstract 3407: Regulation of c-Myc and p53 by splicing factor SRp20

Abstract

Abstract SRp20 is a member of the highly conserved SR protein family of splicing regulators. Our previous study found that SRp20 was overexpressed in ovarian and breast tumors compared to corresponding normal tissues and knockdown of SRp20 expression inhibited tumor cell growth. Suppression of SRp20 by 90% triggered apoptosis of tumor cells through intrinsic pathway, which was accompanied by a downregulation of anti-apoptotic protein, Bcl-2. However, it is unclear what mechanism mediates the induction of apoptosis and downregulation of Bcl-2 by SRp20 knockdown. To address this question, we conducted microarray analysis to identify the genes whose expression or splicing are altered in SRp20-knockdown A2780 cells. Among hundreds of identified genes, the expression of c-Myc and p53 was downregulated. The downregulation was further validated by quantitative PCR. Because of the fundamental importance of p53 and c-Myc in cancer biology and apoptosis, we further examined the expression of these two genes at protein levels. Western blotting showed that p53 is upregulated at protein level in SRp20 knockdown cells, contradictory to its expression at the mRNA level, while the expression of c-Myc is consistent at the protein level and at the mRNA level. These results suggest that SRp20 knockdown-induced apoptosis could be mediated by upregulated p53 protein or reduced c-Myc or both, given already established connection between these two proteins and apoptosis. How SRp20 is involved in the regulation of p53 and c-Myc remains to be determined and is currently under investigation. Citation Format: Xiaolong He, Jilai Yang, Shijie Wang. Regulation of c-Myc and p53 by splicing factor SRp20. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3407. doi:10.1158/1538-7445.AM2014-3407