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

• 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
• DOI: 10.1016/j.oraloncology.2019.04.018
• Texto Completo: http://dx.doi.org/10.1016/j.oraloncology.2019.04.018; http://hdl.handle.net/11449/189023
• topic: Chemotherapy; Drug targets; Integrative analysis; Laryngeal squamous cell carcinoma; miRNAs; mRNA; Treatment

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.