TITLE:
Acetyltransferase P300 Inhibits the Proliferation, Invasion, and Migration of Esophageal Cancer via Survivin Acetylation
AUTHORS:
Jingxiong Zheng, Jingtao Huang, Zongying Liang
KEYWORDS:
P300, Acetyltransferase, Survivin, Acetylation Modification, Esophageal Cancer
JOURNAL NAME:
Chinese Medicine,
Vol.13 No.4,
December
14,
2022
ABSTRACT: Background: Esophageal cancer is one of the primary death causes leading by cancer in the world, which is high morbidity and mortality.Epigenetic acetylation modification participates in and regulates the proliferation, invasion, and metastasis of various tumor cells, and the acetylation modification of tumor proteins involved by acetyltransferases may be one of the important mechanisms of esophageal carcinogenesis.The aim of this study was to investigate the correlation of acetyltransferase P300 and Survivin acetylation in esophageal cancer pathogenesis and its molecular mechanism. Methods: Fifty-five cases of esophageal cancer tissues and adjacent cancer tissues were collected, Survivin and P300 protein expression was measured by immunohistochemistry (SP) and protein blotting (Western Blot); Survivin acetylated protein levels were measured by coimmunoprecipitation (Co-IP); bioinformatics predicted the relationship between P300 and Survivin as the substrate, and fluorescence immunohistochemistry (IF) to verify the localization and expression of Survivin and P300 in esophageal cancer tissues; the correlation of Survivin acetylation, P300 and clinical cases characteristics was analyzed by statistics. P300 siRNA sequences were structured and transfected into EC109 cells. P300 protein expression and Survivin acetylated protein levels were determined by Co-IP. Cell viability was determined by the MTT assay, Scratch healing and Transwellchamber assay examined cell migration and invasion ability. Results: Survivin and P300 protein expression was significantly increased in human esophageal cancer tissues and EC109 cells.The Survivin protein was acetylated in esophageal cancer tissues and EC109 cells, and its protein acetylation rate was significantly increased; bioinformatics predicted that the acetyltransferase P300 could catalyze the acetylation of Survivin as a substrate, and the fluorescence immunohistochemistry confirmed that both Survivin and P300 simultaneously showed a high expression state in cancer tissues; Survivin acetylation and P300 expression; Survivin acetylation and P300 were closely related with esophageal cancer stage, tissue differentiation and lymph node metastasis.The vitro experiments showed that P300 RNA interference in esophageal cancer cells can significantly reduce the Survivin protein acetylation level, while inhibiting the survival, migration and invasion capacity of EC109 cells.Conclusion: P300 has a correlation with Survivin acetylation in the lespathological process of esophageal cancer,P300 may be an important upstream molecule of Survivin acetylation and has an important potential value in the diagnosis and treatment of esophageal cancer.