PMID- 27658780 OWN - NLM STAT- MEDLINE DCOM- 20170228 LR - 20220408 IS - 1423-0380 (Electronic) IS - 1010-4283 (Linking) VI - 37 IP - 11 DP - 2016 Nov TI - HOX genes: potential candidates for the progression of laryngeal squamous cell carcinoma. PG - 15087-15096 AB - Laryngeal squamous cell carcinoma (LSCC) is a very aggressive cancer, considered to be a subtype of the head and neck squamous cell carcinoma (HNSCC). Despite significant advances in the understanding and treatment of cancer, prognosis of patients with LSCC has not improved recently. In the present study, we sought to understand better the genetic mechanisms underlying LSCC development. Thirty-two tumor samples were collected from patients undergoing surgical resection of LSCC. The samples were submitted to whole-genome cDNA microarray analysis aiming to identify genetic targets in LSCC. We also employed bioinformatic approaches to expand our findings using the TCGA database and further performed functional assays, using human HNSCC cell lines, to evaluate viability, cell proliferation, and cell migration after silencing of selected genes. Eight members of the homeobox gene family (HOX) were identified to be overexpressed in LSCC samples when compared to normal larynx tissue. Quantitative RT-PCR analysis validated the overexpression of HOX gene family members in LSCC. Receiver operating characteristic (ROC) statistical method curve showed that the expression level of seven members of HOX gene family can distinguish tumor from nontumor tissue. Correlation analysis of clinical and gene expression data revealed that HOXC8 and HOXD11 genes were associated with the differentiation degree of tumors and regional lymph node metastases, respectively. Additionally, siRNA assays confirmed that HOXC8, HOXD10, and HOXD11 genes might be critical for cell colony proliferation and cell migration. According to our findings, several members of the HOX genes were overexpressed in LSCC samples and seem to be required in biological processes involved in tumor development. This suggests that HOX genes might play a critical role in the physiopathology of LSCC tumors. FAU - de Barros E Lima Bueno, Rafaela AU - de Barros E Lima Bueno R AD - Department of Genetics, Ribeirao Preto Medical School, University of Sao Paulo, Avenida Bandeirantes 3900, Monte Alegre, Ribeirao Preto, SP, CEP: 14049-900, Brazil. AD - National Institute of Science and Technology, Stem Cell and Cell Therapy and Center for Cell Based Therapy, Rua Tenente Catao Roxo, 2501, Monte Alegre, Ribeirao Preto, SP, CEP: 14051-140, Brazil. FAU - Ramao, Anelisa AU - Ramao A AD - Department of Genetics, Ribeirao Preto Medical School, University of Sao Paulo, Avenida Bandeirantes 3900, Monte Alegre, Ribeirao Preto, SP, CEP: 14049-900, Brazil. AD - National Institute of Science and Technology, Stem Cell and Cell Therapy and Center for Cell Based Therapy, Rua Tenente Catao Roxo, 2501, Monte Alegre, Ribeirao Preto, SP, CEP: 14051-140, Brazil. FAU - Pinheiro, Daniel Guariz AU - Pinheiro DG AD - Department of Technology, College of Agriculture and Veterinary Sciences, UNESP, Jaboticabal, SP, CEP: 14884-900, Brazil. FAU - Alves, Cleidson Padua AU - Alves CP AD - National Institute of Science and Technology, Stem Cell and Cell Therapy and Center for Cell Based Therapy, Rua Tenente Catao Roxo, 2501, Monte Alegre, Ribeirao Preto, SP, CEP: 14051-140, Brazil. AD - Center for Integrative Systems Biology, CISBi, NAP/USP, Rua Catao Roxo, 2501, Monte Alegre, Ribeirao Preto, SP, CEP: 14051-140, Brazil. FAU - Kannen, Vinicius AU - Kannen V AD - Department of Pathology, Ribeirao Preto Medical School, University of Sao Paulo, Avenida Bandeirantes 3900, Monte Alegre, Ribeirao Preto, SP, CEP: 14049-900, Brazil. FAU - Jungbluth, Achim A AU - Jungbluth AA AD - Department of Pathology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA. FAU - de Araujo, Luiza Ferreira AU - de Araujo LF AD - Department of Genetics, Ribeirao Preto Medical School, University of Sao Paulo, Avenida Bandeirantes 3900, Monte Alegre, Ribeirao Preto, SP, CEP: 14049-900, Brazil. AD - National Institute of Science and Technology, Stem Cell and Cell Therapy and Center for Cell Based Therapy, Rua Tenente Catao Roxo, 2501, Monte Alegre, Ribeirao Preto, SP, CEP: 14051-140, Brazil. AD - Center for Integrative Systems Biology, CISBi, NAP/USP, Rua Catao Roxo, 2501, Monte Alegre, Ribeirao Preto, SP, CEP: 14051-140, Brazil. FAU - Muys, Bruna Rodrigues AU - Muys BR AD - Department of Genetics, Ribeirao Preto Medical School, University of Sao Paulo, Avenida Bandeirantes 3900, Monte Alegre, Ribeirao Preto, SP, CEP: 14049-900, Brazil. AD - National Institute of Science and Technology, Stem Cell and Cell Therapy and Center for Cell Based Therapy, Rua Tenente Catao Roxo, 2501, Monte Alegre, Ribeirao Preto, SP, CEP: 14051-140, Brazil. FAU - Fonseca, Aline Simoneti AU - Fonseca AS AD - Department of Genetics, Ribeirao Preto Medical School, University of Sao Paulo, Avenida Bandeirantes 3900, Monte Alegre, Ribeirao Preto, SP, CEP: 14049-900, Brazil. AD - National Institute of Science and Technology, Stem Cell and Cell Therapy and Center for Cell Based Therapy, Rua Tenente Catao Roxo, 2501, Monte Alegre, Ribeirao Preto, SP, CEP: 14051-140, Brazil. AD - Center for Integrative Systems Biology, CISBi, NAP/USP, Rua Catao Roxo, 2501, Monte Alegre, Ribeirao Preto, SP, CEP: 14051-140, Brazil. FAU - Placa, Jessica Rodrigues AU - Placa JR AD - National Institute of Science and Technology, Stem Cell and Cell Therapy and Center for Cell Based Therapy, Rua Tenente Catao Roxo, 2501, Monte Alegre, Ribeirao Preto, SP, CEP: 14051-140, Brazil. AD - Center for Integrative Systems Biology, CISBi, NAP/USP, Rua Catao Roxo, 2501, Monte Alegre, Ribeirao Preto, SP, CEP: 14051-140, Brazil. FAU - Panepucci, Rodrigo Alexandre AU - Panepucci RA AD - National Institute of Science and Technology, Stem Cell and Cell Therapy and Center for Cell Based Therapy, Rua Tenente Catao Roxo, 2501, Monte Alegre, Ribeirao Preto, SP, CEP: 14051-140, Brazil. FAU - Neder, Luciano AU - Neder L AD - Department of Pathology, Ribeirao Preto Medical School, University of Sao Paulo, Avenida Bandeirantes 3900, Monte Alegre, Ribeirao Preto, SP, CEP: 14049-900, Brazil. FAU - Saggioro, Fabiano P AU - Saggioro FP AD - Department of Pathology, Ribeirao Preto Medical School, University of Sao Paulo, Avenida Bandeirantes 3900, Monte Alegre, Ribeirao Preto, SP, CEP: 14049-900, Brazil. FAU - Mamede, Rui Celso M AU - Mamede RC AD - Department of Ophthalmology, Otorhinolaryngology and Head and Neck Surgery, Ribeirao Preto Medical School, University of Sao Paulo, Avenida Bandeirantes 3900, Monte Alegre, Ribeirao Preto, SP, CEP: 14049-900, Brazil. FAU - Figueiredo, David Livingstone Alves AU - Figueiredo DL AD - University of Centro-Oeste, Rua Padre Salvador, 875, Santa Cruz, Guarapuava, PR, CEP 85015-430, Brazil. FAU - Silva, Wilson Araujo Jr AU - Silva WA Jr AD - Department of Genetics, Ribeirao Preto Medical School, University of Sao Paulo, Avenida Bandeirantes 3900, Monte Alegre, Ribeirao Preto, SP, CEP: 14049-900, Brazil. wilsonjr@usp.br. AD - National Institute of Science and Technology, Stem Cell and Cell Therapy and Center for Cell Based Therapy, Rua Tenente Catao Roxo, 2501, Monte Alegre, Ribeirao Preto, SP, CEP: 14051-140, Brazil. wilsonjr@usp.br. AD - Center for Integrative Systems Biology, CISBi, NAP/USP, Rua Catao Roxo, 2501, Monte Alegre, Ribeirao Preto, SP, CEP: 14051-140, Brazil. wilsonjr@usp.br. AD - Centro Regional de Hemoterapia de Ribeirao Preto, Rua Catao Roxo, 2501, Monte Alegre, Ribeirao Preto, SP, CEP: 14051-140, Brazil. wilsonjr@usp.br. LA - eng PT - Journal Article DEP - 20160922 PL - Netherlands TA - Tumour Biol JT - Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine JID - 8409922 RN - 0 (Biomarkers, Tumor) RN - 0 (RNA, Messenger) RN - 0 (RNA, Small Interfering) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Apoptosis MH - Biomarkers, Tumor/genetics/*metabolism MH - Carcinoma, Squamous Cell/genetics/metabolism/*pathology MH - Cell Proliferation MH - Disease Progression MH - Female MH - Gene Expression Regulation, Neoplastic MH - Genes, Homeobox/*genetics MH - Humans MH - Immunoenzyme Techniques MH - Laryngeal Neoplasms/genetics/metabolism/*secondary MH - Lymphatic Metastasis MH - Male MH - Middle Aged MH - Neoplasm Recurrence, Local/genetics/metabolism/*pathology MH - RNA, Messenger/genetics MH - RNA, Small Interfering/genetics MH - Real-Time Polymerase Chain Reaction MH - Reverse Transcriptase Polymerase Chain Reaction MH - Tumor Cells, Cultured OTO - NOTNLM OT - Cell migration OT - Gene regulation OT - HOX genes OT - Larynx squamous cell carcinoma EDAT- 2016/09/24 06:00 MHDA- 2017/03/01 06:00 CRDT- 2016/09/24 06:00 PHST- 2016/04/04 00:00 [received] PHST- 2016/09/07 00:00 [accepted] PHST- 2016/09/24 06:00 [pubmed] PHST- 2017/03/01 06:00 [medline] PHST- 2016/09/24 06:00 [entrez] AID - 10.1007/s13277-016-5356-8 [pii] AID - 10.1007/s13277-016-5356-8 [doi] PST - ppublish SO - Tumour Biol. 2016 Nov;37(11):15087-15096. doi: 10.1007/s13277-016-5356-8. Epub 2016 Sep 22.