title: Downregulation of HDAC9 inhibits cell proliferation and tumor formation by inducing cell cycle arrest in retinoblastoma.
abstract: Histone deacetylase 9 (HDAC9) is a member of class II HDACs, which regulates a wide variety of normal and abnormal physiological functions. Recently, HDAC9 has been found to be overexpressed in some types of human cancers. However, the role of HDAC9 in retinoblastoma remains unclear. In this study, we found that HDAC9 was commonly expressed in retinoblastoma tissues and HDAC9 was overexpressed in prognostically poor retinoblastoma patients. Through knocking down HDAC9 in Y79 and WERI-Rb-1 cells, the expression level of HDAC9 was found to be positively related to cell proliferation in vitro. Further investigation indicated that knockdown HDAC9 could significantly induce cell cycle arrest at G1 phase in retinoblastoma cells. Western blot assay showed downregulation of HDAC9 could significantly decrease cyclin E2 and CDK2 expression. Lastly, xenograft study in nude mice showed that downregulation of HDAC9 inhibited tumor growth and development in vivo. Therefore, our results suggest that HDAC9 could serve as a novel potential therapeutic target in the treatment of retinoblastoma.
authors.affiliation: Medical School of Nanjing University, Department of Ophthalmology, Jinling Hospital, Nanjing, 210002, China.
authors.forename: Yiting
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Medical School of Nanjing University, Department of Ophthalmology, Jinling Hospital, Nanjing, 210002, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Wu
authors.affiliation: Medical School of Nanjing University, Department of Ophthalmology, Jinling Hospital, Nanjing, 210002, China.
authors.forename: Fengjie
authors.initials: F
authors.lastname: Xia
authors.affiliation: Medical School of Nanjing University, Department of Ophthalmology, Jinling Hospital, Nanjing, 210002, China.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Xian
authors.affiliation: Medical School of Nanjing University, Department of Ophthalmology, Jinling Hospital, Nanjing, 210002, China.
authors.forename: Xinyue
authors.initials: X
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Silkworm Genome Biology, Institute of Sericulture and Systems Biology, Southwest University, Chongqing, 400716, China. Electronic address: hcui@swu.edu.cn.
authors.forename: Hongjuan
authors.initials: H
authors.lastname: Cui
authors.affiliation: Medical School of Nanjing University, Department of Ophthalmology, Jinling Hospital, Nanjing, 210002, China. Electronic address: huangzhenping19633@163.com.
authors.forename: Zhenping
authors.initials: Z
authors.lastname: Huang
mesh_terms: D000818:Animals; D059447:Cell Cycle Checkpoints; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002648:Child; D002675:Child, Preschool; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006655:Histone Deacetylases / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D051379:Mice; D008819:Mice, Nude; D011379:Prognosis; D012097:Repressor Proteins / Q000235:genetics*; D012160:Retina / Q000378:metabolism / Q000473:pathology*; D019572:Retinal Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D012175:Retinoblastoma / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology
chemical_list: D012097:Repressor Proteins; C486544:HDAC9 protein, human; C486545:Hdac9 protein, mouse; D006655:Histone Deacetylases
keywords: Cell cycle; Cell proliferation; HDAC9; Retinoblastoma; Tumor formation