title: PROX1 gene is differentially expressed in oral cancer and reduces cellular proliferation.
abstract: Homeobox genes are a family of transcription factors that play a pivotal role in embryogenesis. Prospero homeobox 1 (PROX1) has been shown to function as a tumor suppressor gene or oncogene in various types of cancer, including oral squamous cell carcinoma (OSCC). We have previously identified PROX1 as a downregulated gene in OSCC. The aim of this study is to clarify the underlying mechanism by which PROX1 regulates tumorigenicity of OSCC cells. PROX1 mRNA and protein expression levels were first investigated in 40 samples of OSCC and in nontumor margins. Methylation and amplification analysis was also performed to assess the epigenetic and genetic mechanisms involved in controlling PROX1 expression. OSCC cell line SCC9 was also transfected to stably express the PROX1 gene. Next, SCC9-PROX1-overexpressing cells and controls were subjected to proliferation, differentiation, apoptosis, migration, and invasion assays in vitro. OSCC samples showed reduced PROX1 expression levels compared with nontumor margins. PROX1 amplification was associated with better overall survival. PROX1 overexpression reduces cell proliferation and downregulates cyclin D1. PROX1-overexpressing cells also exhibited reduced CK18 and CK19 expression and transcriptionally altered the expression of WISP3, GATA3, NOTCH1, and E2F1. Our results suggest that PROX1 functions as a tumor suppressor gene in oral carcinogenesis.
authors.affiliation: From the Department of Estomatology (MFSDR, LAR, FDN), School of Dentistry; Department of Biochemistry (KBP), Chemistry Institute; Department of Head and Neck Surgery (RAM), School of Medicine; Department of Epidemiology (RML), Public Health; Department of Genetics and Evolutionary Biology (EHT), Institute of Biosciences, University of São Paulo; Albert Einstein Research and Education Institute (PS), Albert Einstein Israelita Hospital, Center for Experimental Research; Department of Head and Neck Surgery (RDC), Arnaldo Vieira de Carvalho Cancer Institute; Department of Head and Neck Surgery (MBC), Heliopolis Hospital Complex, São Paulo; Department of Estomatology (FCdAX), School of Dentistry, Federal University of Bahia, Salvador; Department of Histology (CdOR), School of Dentistry, University of São Paulo, Bauru; and Department of Molecular Biology (EHT), School of Medicine, São José do Rio Preto, Brazil.
authors.forename: Maria F S D
authors.initials: MFSD
authors.lastname: Rodrigues
authors.forename: Camila
authors.initials: C
authors.lastname: de Oliveira Rodini
authors.forename: Flávia C
authors.initials: FC
authors.lastname: de Aquino Xavier
authors.forename: Katiúcia B
authors.initials: KB
authors.lastname: Paiva
authors.forename: Patrícia
authors.initials: P
authors.lastname: Severino
authors.forename: Raquel A
authors.initials: RA
authors.lastname: Moyses
authors.forename: Rossana M
authors.initials: RM
authors.lastname: López
authors.forename: Rafael
authors.initials: R
authors.lastname: DeCicco
authors.forename: Lília A
authors.initials: LA
authors.lastname: Rocha
authors.forename: Marcos B
authors.initials: MB
authors.lastname: Carvalho
authors.forename: Eloiza H
authors.initials: EH
authors.lastname: Tajara
authors.forename: Fabio D
authors.initials: FD
authors.lastname: Nunes
mesh_terms: D000328:Adult; D017209:Apoptosis; D015153:Blotting, Western; D049109:Cell Proliferation; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009061:Mouth Mucosa / Q000378:metabolism / Q000473:pathology; D009062:Mouth Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012334:RNA, Neoplasm / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis / Q000235:genetics*; D000098551:Prospero-Related Homeobox 1 Protein
chemical_list: D018398:Homeodomain Proteins; D012334:RNA, Neoplasm; D025521:Tumor Suppressor Proteins; D000098551:Prospero-Related Homeobox 1 Protein