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Polycomb Repressive Complex 2 (PRC2) member enhancer of zeste homologue 2 (EZH2) trimethylates histone H3 lysine 27 (H3K27me3), alters chromatin structure and contributes to epigenetic regulation of gene expression in normal and disease processes. Phosphorylation of EZH2 augmented EZH2 oncogenic activity in cancer but observations have been limited to serine 21 (S21) residue by protein kinase B. In addition, phosphorylation of the evolutionarily conserved T372 motif of EZH2 by p38 resulted in EZH2 interaction with Ying Yang 1 and promoted muscle stem cell differentiation. In the present study, we used epithelial ovarian cancer (OC) cells as a model to demonstrate that phosphorylation of EZH2 at T372 by protein kinase A (PKA) induced a dominant-negative EZH2 phenotype, inhibited OC cell proliferation and migration in vitro and decreased ovarian xenograft tumor growth in vivo. Phosphorylation of T372 by PKA enhanced the interaction between EZH2 and signal transducer and activator of transcription 3 (STAT3), and STAT3 binding to pT372-EZH2 reduced cellular levels of pSTAT3 and downregulated interleukin 6 receptor expression in OC. Furthermore, PKA-mediated pT372-EZH2 decreased ATP levels and altered mitochondrial gene expression, resulting in mitochondrial dysfunction and reduced OC cell growth. These findings demonstrate that PKA-mediated T372 phosphorylation reduces oncogenic EZH2 activity and reveal a novel role for pT372 in regulating EZH2 in OC and possibly other cancers.

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Introduction The purpose of this study was to determine the predictive and prognostic factors for COVID‐19 infection and its relationship with human leukocyte antigen (HLA) in kidney transplant recipients. Material and method Three hundred fifty kidney transplant recipients were included in the study. Recipients were divided into two groups: COVID‐19(+) (n = 100) and control (n = 250). The relationships between HLA frequencies, COVID‐19 infection, and prognostic factors (age, donor type, immunosuppression protocol, etc.) were then evaluated. Logistic regression analysis, heatmap, and decision tree methods were used to determine predictive and prognostic factors. The study was performed retrospectively. Results Advanced age and deceased transplantation emerged as predictive of SARS‐CoV‐2 infection, while the presence of HLA‐A*11, the HLA match ratio, and high‐dose tacrolimus were identified as prognostic factors in kidney transplant recipients. HLA‐A10, HLA‐B*13, HLA‐B22, and HLA‐B*55 were shown to be associated with SARS‐CoV‐2 infection at univariate analysis, and HLA‐B*57, HLA‐DRB1*11, and HLA‐DRB1*13 at logistic regression analysis. Conclusion HLA‐A10, HLA‐B*13, HLA‐B*55, HLA‐B*57, HLA‐DRB1*11, and HLA‐DRB1*13 were identified for the first time in the literature associated with SARS‐CoV‐2 infection in kidney transplant recipients.