CHI-KAT8i5 suppresses ESCC tumor growth through inhibiting KAT8 mediate c-Myc stability
The integrated analysis of histone modifier enzymes in solid tumor, especially in esophageal squamous cell carcinoma (ESCC) is still inadequate. Here, we investigate the expression levels of histone modifier enzymes in ESCC tissues. Notably, KAT8 is identified as a prognostic and therapeutic biomarker in ESCC. Esophageal tissue-specific deletion of KAT8 mice exhibite less tumor burden after induction of tumorigenesis via 4NQO treatment compared with wild-type mice. Meanwhile, silencing KAT8 significantly suppresses tumor growth in CDX and PDX model. Mechanically, we confirm that KAT8 regulates c-Myc protein stability by directly binding it. Furthermore, we design and screen a specific KAT8 inhibitor (CHI-KAT8i5) that significantly attenuate tumor growth in vitro and in vivo, providing promising potential for clinical application. Thus, our work identify KAT8 could serve as a potential clinically relevant biomarker and therapeutic target in patients with ESCC disease and optimize KAT8 inhibitor is a promising lead candidate for ESCC therapy. Overall design: To investigate the potential mechanism of KAT8.The scramble and shKAT8  cell line were used for transcriptome sequencing.