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

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Autor(es): dc.contributorUniversidade Estadual Paulista (UNESP)-
Autor(es): dc.creatorLapa, Rainer Marco Lopez-
Autor(es): dc.creatorBarros-Filho, Mateus Camargo-
Autor(es): dc.creatorMarchi, Fabio Albuquerque-
Autor(es): dc.creatorDomingues, Maria Aparecida Custódio-
Autor(es): dc.creatorde Carvalho, Genival Barbosa-
Autor(es): dc.creatorDrigo, Sandra Aparecida-
Autor(es): dc.creatorKowalski, Luiz Paulo-
Autor(es): dc.creatorRogatto, Silvia Regina-
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Descrição: dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)-
Descrição: dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)-
Descrição: dc.descriptionCNPq: 153142/2012-0-
Descrição: dc.descriptionProcesso FAPESP: 2008/57887-9-
Descrição: dc.descriptionCNPq: 573589/08-9-
Descrição: dc.descriptionObjectives: 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.-
Formato: dc.format76-84-
Idioma: dc.languageen-
Relação: dc.relationOral Oncology-
Direitos: dc.rightsopenAccess-
Palavras-chave: dc.subjectChemotherapy-
Palavras-chave: dc.subjectDrug targets-
Palavras-chave: dc.subjectIntegrative analysis-
Palavras-chave: dc.subjectLaryngeal squamous cell carcinoma-
Palavras-chave: dc.subjectmiRNAs-
Palavras-chave: dc.subjectmRNA-
Palavras-chave: dc.subjectTreatment-
Título: dc.titleIntegrated miRNA and mRNA expression analysis uncovers drug targets in laryngeal squamous cell carcinoma patients-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional - Unesp

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