title: HOXA10 controls proliferation, migration and invasion in oral squamous cell carcinoma.
abstract: Although HOX genes are best known for acting in the regulation of important events during embryogenesis, including proliferation, differentiation and migration, alterations in their expression patterns have been frequently described in cancers. In previous studies we analyzed the expression profile of the members of the HOX family of homeobox genes in oral samples of normal mucosa and squamous cell carcinoma (OSCC) and identified differently expressed genes such as HOXA10. The present study aimed to validate the increased expression of HOXA10 in OSCCs, and to investigate the effects arising from its knockdown in OSCC cells. The levels of HOXA10 mRNA were determined in human OSCC samples and cell lines by quantitative PCR, and HOXA10-mediated effects on proliferation, apoptosis, adhesion, epithelial-mesenchymal transition (EMT), migration and invasion were studied in HSC-3 tongue carcinoma cells by using retrovirus-mediated RNA interference. Higher expression of HOXA10 mRNA was observed in OSCC cell lines and in tumor tissues compared to normal controls. HOXA10 knockdown significantly reduced the proliferation of the tumor cells which was accompanied by increased levels of p21. HOXA10 silencing also significantly induced the expression of EMT markers and enhanced the adhesion, migration and invasion of HSC-3 cells. No effects on cell death were observed after HOXA10 knockdown. The results of the current study confirm the overexpression of HOXA10 in OSCCs, and further demonstrate that its expression is functionally associated with several important biological processes related to oral tumorigenesis, such as proliferation, migration and invasion.
authors.affiliation: Department of Oral Diagnosis, School of Dentistry, University of Campinas Piracicaba, São Paulo, Brazil ; Department of Life Sciences, Bahia State University Bahia, Brazil.
authors.forename: Manoela
authors.initials: M
authors.lastname: Carrera
authors.affiliation: Department of Diagnostics and Oral Medicine, Institute of Dentistry, and Medical Research Center, Oulu University Hospital Oulu, Finland.
authors.forename: Carolina C
authors.initials: CC
authors.lastname: Bitu
authors.affiliation: Department of Oral Diagnosis, School of Dentistry, University of Campinas Piracicaba, São Paulo, Brazil.
authors.forename: Carine Ervolino
authors.initials: CE
authors.lastname: de Oliveira
authors.affiliation: Department of Oral Diagnosis, School of Dentistry, University of Campinas Piracicaba, São Paulo, Brazil ; Department of Clinical, Faculty of Medicine of Jundiai Jundiai, São Paulo, Brazil.
authors.forename: Nilva K
authors.initials: NK
authors.lastname: Cervigne
authors.affiliation: Department of Oral Diagnosis, School of Dentistry, University of Campinas Piracicaba, São Paulo, Brazil.
authors.forename: Edgard
authors.initials: E
authors.lastname: Graner
authors.affiliation: Oulu Center for Cell-Matrix Research, Faculty of Biochemistry and Molecular Medicine, University of Oulu Finland.
authors.forename: Aki
authors.initials: A
authors.lastname: Manninen
authors.affiliation: Department of Oral Diagnosis, School of Dentistry, University of Campinas Piracicaba, São Paulo, Brazil ; Department of Diagnostics and Oral Medicine, Institute of Dentistry, and Medical Research Center, Oulu University Hospital Oulu, Finland ; Institute of Dentistry, University of Helsinki Finland.
authors.forename: Tuula
authors.initials: T
authors.lastname: Salo
authors.affiliation: Department of Oral Diagnosis, School of Dentistry, University of Campinas Piracicaba, São Paulo, Brazil.
authors.forename: Ricardo D
authors.initials: RD
authors.lastname: Coletta
mesh_terms: D017209:Apoptosis; D063646:Carcinogenesis; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D058750:Epithelial-Mesenchymal Transition; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D000080905:Homeobox A10 Proteins; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009062:Mouth Neoplasms / Q000473:pathology*; D009361:Neoplasm Invasiveness; D034622:RNA Interference
chemical_list: D000080905:Homeobox A10 Proteins; D018398:Homeodomain Proteins; C069634:HOXA10 protein, human
keywords: HOXA10; Oral squamous cell carcinoma; invasion; migration; p21; proliferation; tumorigenesis