Autor(es): 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]
Data: 2019
Identificador Persistente: http://hdl.handle.net/11449/189023
Origem: Oasisbr
Assunto(s): Chemotherapy; Drug targets; Integrative analysis; Laryngeal squamous cell carcinoma; miRNAs; mRNA; Treatment
Made available in DSpace on 2019-10-06T16:27:20Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-06-01
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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.
International Research Center CIPE – A.C.Camargo Cancer Center
Department of Genetics Institute of Bioscience São Paulo State University – UNESP
Department of Pathology Faculty of Medicine São Paulo State University-UNESP
Department of Head and Neck Surgery and Otorhinolaryngology A.C.Camargo Cancer Center
Department of Surgery and Orthopedics Faculty of Medicine São Paulo State University - UNESP
Department of Clinical Genetics Vejle Hospital Institute of Regional Health Research University of Southern Denmark
Department of Genetics Institute of Bioscience São Paulo State University – UNESP
Department of Pathology Faculty of Medicine São Paulo State University-UNESP
Department of Surgery and Orthopedics Faculty of Medicine São Paulo State University - UNESP
CNPq: 153142/2012-0
FAPESP: 2008/57887-9
CNPq: 573589/08-9
