title: RNAi screening identifies HAT1 as a potential drug target in esophageal squamous cell carcinoma.
abstract: Esophageal carcinoma (EC) is one of the most fatal carcinomas of the gastrointestinal tract. Aberrant activity of histone acetyltransferases (HATs)/deacetylases (HDACs) play a critical role in carcinogenesis through the regulation of the genes involved in cell differentiation, proliferation, and apoptosis. However, cellular functions of HATs/HDACs in esophageal cancer and its molecular mechanisms remain unclear. An RNAi screen was used in this study to identify the histone acetyltransferases (HATs) and deacetylases (HDACs) that could be critical for the survival of EC cells. We demonstrated that HAT1 (histone acetyltransferase 1) was an important determinant to regulate the proliferation of human EC Eca-109 cells. Furthermore, we showed that the knockdown of HAT1 induced a G2/M cell cycle arrest, which was associated with the disruption of cell cycle-related events, including the decrease of cyclinD1 as well as alteration in cyclinB1 expression. The expression of HAT1 was validated to be higher in the primary tumors and adjacent tissue as compared to that of the normal esophageal tissue. Furthermore, we found that HAT1 expression was directly correlated with the poor tumor differentiation of EC tissue, which suggested that HAT1 played an important role in esophageal carcinoma and that it could be a novel EC therapeutic target.
authors.affiliation: Department of Thoracic Surgery, Zhongshan Hospital Shanghai 200032, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Xue
authors.affiliation: Department of Pathology, Zhongshan Hospital Shanghai 200032, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Hou
authors.affiliation: Department of Thoracic Surgery, Zhongshan Hospital Shanghai 200032, China.
authors.forename: Qun
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Thoracic Surgery, Zhongshan Hospital Shanghai 200032, China.
authors.forename: Liqing
authors.initials: L
authors.lastname: Yao
authors.affiliation: Department of Thoracic Surgery, Zhongshan Hospital Shanghai 200032, China.
authors.forename: Songtao
authors.initials: S
authors.lastname: Xu
authors.affiliation: Department of Thoracic Surgery, Zhongshan Hospital Shanghai 200032, China.
authors.forename: Di
authors.initials: D
authors.lastname: Ge
mesh_terms: D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D045744:Cell Line, Tumor; D004938:Esophageal Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D005434:Flow Cytometry; D051548:Histone Acetyltransferases / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D011379:Prognosis; D034622:RNA Interference; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D034741:RNA, Small Interfering; D051548:Histone Acetyltransferases; C110880:histone acetyltransferase type B complex
keywords: Esophageal carcinoma; G2-M; HAT1; RNAi screen; tumor differentiation