Integrated miRNA and mRNA expression analysis uncovers drug targets in laryngeal squamous cell carcinoma patients
Autor(a) principal: | |
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Data de Publicação: | 2019 |
Outros Autores: | , , , , , , |
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. |
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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 |