Figure 6
From: Multiple genetic mutations caused by NKX6.3 depletion contribute to gastric tumorigenesis
NKX6.3 expression is inversely correlated with AICDA/APOBEC gene family and DNA repair genes in both gastric cancers and non-cancerous gastric mucosae. (A) mRNA expression levels of NKX6.3, AICDA, NFκB p65, CBFβ, APOBEC3A and APOBEC3B in H. pylori CagA positive gastric mucosae compared to those in H. pylori CagA negative gastric mucosae (n = 55, triplicated experiments). Error bars, SD. P values were derived from t tests. **P < 0.01; ****P < 0.0001. (B) Protein levels of NKX6.3 and mRNA expression levels of AICDA, NFκB p65, CBFβ, and APOBEC3 in gastric mucosa tissues from H. pylori-infected mice (Ctrl, n = 2; H.P, n = 3, triplicated experiments). Error bars, SD. P values were derived from t tests. *P < 0.05; **P < 0.01; ***P < 0.001. (C) mRNA expression levels of AICDA, NFκB p65, CBFβ, APOBEC3A, APOBEC3B, CDH1, CDKN1A, EP300, RhoA, ROCK1, ROCK2, PIK3CA, and CCND1 in gastric cancers with negative and positive NKX6.3 expression (upper panel) and in H. pylori CagA positive and negative gastric mucosae (lower panel) (n = 65, triplicated experiments). Error bars, SD. P values were derived from t tests. n.s, not significant (P > 0.05); **P < 0.01; ***P < 0.001; ****P < 0.0001. (D) Expression of NKX6.3, p53, AICDA, and EP300 proteins in gastric cancers (n = 151) by immunohistochemistry. (E) Kaplan-Meier curves for overall survival of patients (n = 151) with gastric cancer with expression levels of NKX6.3, p53, EP300, and AICDA proteins. (F) Schematic model showing that NKX6.3 depletion in gastric epithelial cells induces mutagenesis of various genes by increasing APOBEC/AICDA activity through enhancing NFκB and CBFβ, finally resulting in the development of gastric cancer.
