title: Overexpression of HDAC9 promotes oral squamous cell carcinoma growth, regulates cell cycle progression, and inhibits apoptosis.
abstract: Histone deacetylases (HDACs) are a family of deacetylase enzymes that regulate the acetylation state of histones and a variety of other non-histone proteins including key oncogenic and tumor suppressor proteins, which modulates chromatin conformation, leading to regulation of gene expression. HDACs has been grouped into classes I-IV and histone deacetylase 9 (HDAC9) belongs to class IIa which exhibits tissue-specific expression. Recent reports have demonstrated both pro-oncogenic and tumor suppressive role for HDAC9 in different cancers; however, its role in OSCC remains elusive. Here, we investigated the role of HDAC9 in pathogenesis of oral squamous cell carcinoma (OSCC). Our data showed significantly increased mRNA and protein expression of HDAC9 in clinical OSCC samples and UPCI-SCC-116 cells as compared to normal counterpart. Kaplan-Meier analysis showed that the patients with high-level of HDAC9 expression had significantly reduced overall survival than those with low-level of HDAC9 expression (p = 0.034). Knockdown of HDAC9 using siRNA interference suppressed cell proliferation, increased apoptosis, and induced G0/G1 cell cycle arrest in UPCI-SCC-116 cells. Immunofluorescence analysis showed increased nuclear localization of HDAC9 in frozen OSCC sections, and indicative of active HDAC9 that may transcriptionally repress its downstream target genes. Subsequent investigation revealed that overexpression of HDAC9 contributes to OSCC carcinogenesis via targeting a transcription factor, MEF2D, and NR4A1/Nur77, a pro-apoptotic MEF2 target.
authors.affiliation: Department of Otolaryngology and Head and Neck Surgery, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012, India.
authors.forename: Bhawna
authors.initials: B
authors.lastname: Rastogi
authors.affiliation: Department of Experimental Medicine and Biotechnology, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012, India.
authors.forename: Satish K
authors.initials: SK
authors.lastname: Raut
authors.affiliation: Department of Otolaryngology and Head and Neck Surgery, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012, India.
authors.forename: Naresh K
authors.initials: NK
authors.lastname: Panda
authors.affiliation: Department of Oral Health Sciences Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012, India.
authors.forename: Vidya
authors.initials: V
authors.lastname: Rattan
authors.affiliation: Department of Histopathology, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012, India.
authors.forename: Bishan D
authors.initials: BD
authors.lastname: Radotra
authors.affiliation: Department of Experimental Medicine and Biotechnology, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012, India. madhu.khullar@gmail.com.
authors.forename: Madhu
authors.initials: M
authors.lastname: Khullar
mesh_terms: D000328:Adult; D017209:Apoptosis; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000473:pathology*; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000201:enzymology / Q000473:pathology*; D012097:Repressor Proteins / Q000378:metabolism*
chemical_list: D012097:Repressor Proteins; C486544:HDAC9 protein, human; D006655:Histone Deacetylases
keywords: HDAC9; MEF2D; NR4A1/Nur77; Oral squamous cell carcinoma