Integrated miRNA and mRNA expression analysis uncovers drug targets in laryngeal squamous cell carcinoma patients

Detalhes bibliográficos
Autor(a) principal: Lapa, Rainer Marco Lopez [UNESP]
Data de Publicação: 2019
Outros Autores: Barros-Filho, Mateus Camargo, Marchi, Fabio Albuquerque, Domingues, Maria Aparecida Custódio [UNESP], de Carvalho, Genival Barbosa, Drigo, Sandra Aparecida [UNESP], Kowalski, Luiz Paulo, Rogatto, Silvia Regina [UNESP]
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNESP
Texto Completo: http://dx.doi.org/10.1016/j.oraloncology.2019.04.018
http://hdl.handle.net/11449/189023
Resumo: Objectives: The current treatment of laryngeal squamous cell carcinoma (LSCC)is based on radical surgery and radiotherapy resulting in high morbidity. Chemoradiotherapy has been used as alternative to organ sparing; however, several advanced cases presented resistance to treatment, which contributes to a high risk of recurrence and mortality. Coding RNAs and miRNAs have potential to be used as biomarkers or targets for cancer therapy. Materials and Methods: In this study, 36 LSCC and 5 non-neoplastic control samples were investigated using miRNA and mRNA large-scale expression analysis and a cross-validation was performed using the TCGA database (116 LSCC and 12 surrounding normal tissues). Results: The large-scale profiling revealed the involvement of 28 miRNAs and 817 genes differentially expressed in LSCC. An integrative analysis comprising predicted and experimentally validated miRNA/mRNA interactions (negatively correlated), resulted in 28 miRNAs and 543 mRNAs. Decreased expression of miR-199b was significantly associated with shorter disease-free survival in LSCC (internal and TCGA datasets). The expression levels of selected miRNAs (miR-199b-5p, miR-29c-3p, miR-204-5p, miR-125b-5p and miR-92a-3p)and genes (COL3A1, COL10A1, ERBB4, HMGA2, HLF, TOP2A, MMP3, MMP13, MMP10 and PPP1R3)were confirmed as altered in LSCC by RT-qPCR. Additionally, a drug target prediction analysis revealed drug combinations based on miRNA and mRNA expression, pointing out novel alternatives to optimize the LSCC treatment. Conclusion: Collectively, these findings provide new insights in the LSCC transcriptional deregulation and potential drug targets.
id UNSP_d72193af6f54147eae8c67fc2568730c
oai_identifier_str oai:repositorio.unesp.br:11449/189023
network_acronym_str UNSP
network_name_str Repositório Institucional da UNESP
repository_id_str 2946
spelling Integrated miRNA and mRNA expression analysis uncovers drug targets in laryngeal squamous cell carcinoma patientsChemotherapyDrug targetsIntegrative analysisLaryngeal squamous cell carcinomamiRNAsmRNATreatmentObjectives: The current treatment of laryngeal squamous cell carcinoma (LSCC)is based on radical surgery and radiotherapy resulting in high morbidity. Chemoradiotherapy has been used as alternative to organ sparing; however, several advanced cases presented resistance to treatment, which contributes to a high risk of recurrence and mortality. Coding RNAs and miRNAs have potential to be used as biomarkers or targets for cancer therapy. Materials and Methods: In this study, 36 LSCC and 5 non-neoplastic control samples were investigated using miRNA and mRNA large-scale expression analysis and a cross-validation was performed using the TCGA database (116 LSCC and 12 surrounding normal tissues). Results: The large-scale profiling revealed the involvement of 28 miRNAs and 817 genes differentially expressed in LSCC. An integrative analysis comprising predicted and experimentally validated miRNA/mRNA interactions (negatively correlated), resulted in 28 miRNAs and 543 mRNAs. Decreased expression of miR-199b was significantly associated with shorter disease-free survival in LSCC (internal and TCGA datasets). The expression levels of selected miRNAs (miR-199b-5p, miR-29c-3p, miR-204-5p, miR-125b-5p and miR-92a-3p)and genes (COL3A1, COL10A1, ERBB4, HMGA2, HLF, TOP2A, MMP3, MMP13, MMP10 and PPP1R3)were confirmed as altered in LSCC by RT-qPCR. Additionally, a drug target prediction analysis revealed drug combinations based on miRNA and mRNA expression, pointing out novel alternatives to optimize the LSCC treatment. Conclusion: Collectively, these findings provide new insights in the LSCC transcriptional deregulation and potential drug targets.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)International Research Center CIPE – A.C.Camargo Cancer CenterDepartment of Genetics Institute of Bioscience São Paulo State University – UNESPDepartment of Pathology Faculty of Medicine São Paulo State University-UNESPDepartment of Head and Neck Surgery and Otorhinolaryngology A.C.Camargo Cancer CenterDepartment of Surgery and Orthopedics Faculty of Medicine São Paulo State University - UNESPDepartment of Clinical Genetics Vejle Hospital Institute of Regional Health Research University of Southern DenmarkDepartment of Genetics Institute of Bioscience São Paulo State University – UNESPDepartment of Pathology Faculty of Medicine São Paulo State University-UNESPDepartment of Surgery and Orthopedics Faculty of Medicine São Paulo State University - UNESPCNPq: 153142/2012-0FAPESP: 2008/57887-9CNPq: 573589/08-9CIPE – A.C.Camargo Cancer CenterUniversidade Estadual Paulista (Unesp)A.C.Camargo Cancer CenterUniversity of Southern DenmarkLapa, Rainer Marco Lopez [UNESP]Barros-Filho, Mateus CamargoMarchi, Fabio AlbuquerqueDomingues, Maria Aparecida Custódio [UNESP]de Carvalho, Genival BarbosaDrigo, Sandra Aparecida [UNESP]Kowalski, Luiz PauloRogatto, Silvia Regina [UNESP]2019-10-06T16:27:20Z2019-10-06T16:27:20Z2019-06-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article76-84http://dx.doi.org/10.1016/j.oraloncology.2019.04.018Oral Oncology, v. 93, p. 76-84.1879-05931368-8375http://hdl.handle.net/11449/18902310.1016/j.oraloncology.2019.04.0182-s2.0-850647311700585723113037140Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengOral Oncologyinfo:eu-repo/semantics/openAccess2024-08-14T14:19:19Zoai:repositorio.unesp.br:11449/189023Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-14T14:19:19Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv Integrated miRNA and mRNA expression analysis uncovers drug targets in laryngeal squamous cell carcinoma patients
title Integrated miRNA and mRNA expression analysis uncovers drug targets in laryngeal squamous cell carcinoma patients
spellingShingle Integrated miRNA and mRNA expression analysis uncovers drug targets in laryngeal squamous cell carcinoma patients
Lapa, Rainer Marco Lopez [UNESP]
Chemotherapy
Drug targets
Integrative analysis
Laryngeal squamous cell carcinoma
miRNAs
mRNA
Treatment
title_short Integrated miRNA and mRNA expression analysis uncovers drug targets in laryngeal squamous cell carcinoma patients
title_full Integrated miRNA and mRNA expression analysis uncovers drug targets in laryngeal squamous cell carcinoma patients
title_fullStr Integrated miRNA and mRNA expression analysis uncovers drug targets in laryngeal squamous cell carcinoma patients
title_full_unstemmed Integrated miRNA and mRNA expression analysis uncovers drug targets in laryngeal squamous cell carcinoma patients
title_sort Integrated miRNA and mRNA expression analysis uncovers drug targets in laryngeal squamous cell carcinoma patients
author Lapa, Rainer Marco Lopez [UNESP]
author_facet Lapa, Rainer Marco Lopez [UNESP]
Barros-Filho, Mateus Camargo
Marchi, Fabio Albuquerque
Domingues, Maria Aparecida Custódio [UNESP]
de Carvalho, Genival Barbosa
Drigo, Sandra Aparecida [UNESP]
Kowalski, Luiz Paulo
Rogatto, Silvia Regina [UNESP]
author_role author
author2 Barros-Filho, Mateus Camargo
Marchi, Fabio Albuquerque
Domingues, Maria Aparecida Custódio [UNESP]
de Carvalho, Genival Barbosa
Drigo, Sandra Aparecida [UNESP]
Kowalski, Luiz Paulo
Rogatto, Silvia Regina [UNESP]
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv CIPE – A.C.Camargo Cancer Center
Universidade Estadual Paulista (Unesp)
A.C.Camargo Cancer Center
University of Southern Denmark
dc.contributor.author.fl_str_mv Lapa, Rainer Marco Lopez [UNESP]
Barros-Filho, Mateus Camargo
Marchi, Fabio Albuquerque
Domingues, Maria Aparecida Custódio [UNESP]
de Carvalho, Genival Barbosa
Drigo, Sandra Aparecida [UNESP]
Kowalski, Luiz Paulo
Rogatto, Silvia Regina [UNESP]
dc.subject.por.fl_str_mv Chemotherapy
Drug targets
Integrative analysis
Laryngeal squamous cell carcinoma
miRNAs
mRNA
Treatment
topic Chemotherapy
Drug targets
Integrative analysis
Laryngeal squamous cell carcinoma
miRNAs
mRNA
Treatment
description Objectives: The current treatment of laryngeal squamous cell carcinoma (LSCC)is based on radical surgery and radiotherapy resulting in high morbidity. Chemoradiotherapy has been used as alternative to organ sparing; however, several advanced cases presented resistance to treatment, which contributes to a high risk of recurrence and mortality. Coding RNAs and miRNAs have potential to be used as biomarkers or targets for cancer therapy. Materials and Methods: In this study, 36 LSCC and 5 non-neoplastic control samples were investigated using miRNA and mRNA large-scale expression analysis and a cross-validation was performed using the TCGA database (116 LSCC and 12 surrounding normal tissues). Results: The large-scale profiling revealed the involvement of 28 miRNAs and 817 genes differentially expressed in LSCC. An integrative analysis comprising predicted and experimentally validated miRNA/mRNA interactions (negatively correlated), resulted in 28 miRNAs and 543 mRNAs. Decreased expression of miR-199b was significantly associated with shorter disease-free survival in LSCC (internal and TCGA datasets). The expression levels of selected miRNAs (miR-199b-5p, miR-29c-3p, miR-204-5p, miR-125b-5p and miR-92a-3p)and genes (COL3A1, COL10A1, ERBB4, HMGA2, HLF, TOP2A, MMP3, MMP13, MMP10 and PPP1R3)were confirmed as altered in LSCC by RT-qPCR. Additionally, a drug target prediction analysis revealed drug combinations based on miRNA and mRNA expression, pointing out novel alternatives to optimize the LSCC treatment. Conclusion: Collectively, these findings provide new insights in the LSCC transcriptional deregulation and potential drug targets.
publishDate 2019
dc.date.none.fl_str_mv 2019-10-06T16:27:20Z
2019-10-06T16:27:20Z
2019-06-01
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://dx.doi.org/10.1016/j.oraloncology.2019.04.018
Oral Oncology, v. 93, p. 76-84.
1879-0593
1368-8375
http://hdl.handle.net/11449/189023
10.1016/j.oraloncology.2019.04.018
2-s2.0-85064731170
0585723113037140
url http://dx.doi.org/10.1016/j.oraloncology.2019.04.018
http://hdl.handle.net/11449/189023
identifier_str_mv Oral Oncology, v. 93, p. 76-84.
1879-0593
1368-8375
10.1016/j.oraloncology.2019.04.018
2-s2.0-85064731170
0585723113037140
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Oral Oncology
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 76-84
dc.source.none.fl_str_mv Scopus
reponame:Repositório Institucional da UNESP
instname:Universidade Estadual Paulista (UNESP)
instacron:UNESP
instname_str Universidade Estadual Paulista (UNESP)
instacron_str UNESP
institution UNESP
reponame_str Repositório Institucional da UNESP
collection Repositório Institucional da UNESP
repository.name.fl_str_mv Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)
repository.mail.fl_str_mv
_version_ 1808128183659134976