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

• Published in: Oral oncology Vol. 93; pp. 76 - 84
• Main Authors: Lapa, Rainer Marco Lopez, Barros-Filho, Mateus Camargo, Marchi, Fabio Albuquerque, Domingues, Maria Aparecida Custódio, de Carvalho, Genival Barbosa, Drigo, Sandra Aparecida, Kowalski, Luiz Paulo, Rogatto, Silvia Regina
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.06.2019
• Subjects: Biomarkers, Tumor - genetics; Carcinoma, Squamous Cell - genetics; Chemotherapy; Down-Regulation; Drug targets; Female; Gene Expression Profiling - methods; Gene Expression Regulation, Neoplastic; Gene Regulatory Networks; Humans; Integrative analysis; Laryngeal Neoplasms - genetics; Laryngeal squamous cell carcinoma; Male; MicroRNAs - genetics; miRNAs; Molecular Targeted Therapy; mRNA; RNA, Messenger - genetics; Survival Analysis; Treatment; Integrative analysis; Chemotherapy; Treatment; miRNAs; Drug targets; Laryngeal squamous cell carcinoma; mRNA
• ISSN: 1368-8375; 1879-0593
• DOI: 10.1016/j.oraloncology.2019.04.018

•Integrated analysis revealed interaction between miRNAs and mRNAs in LSCC.•Five miRNA and 10 mRNA were confirmed as differentially expressed by RT-qPCR.•Drug target prediction analysis revealed new treatment options for LSCC patients.•Inhibitors of matrix extracellular are potential alternative treatments for LSCC.•Most drug targets herein described could be used in the clinical practice. 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. 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). 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. Collectively, these findings provide new insights in the LSCC transcriptional deregulation and potential drug targets.