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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Lopez Lapa, Rainer Marco [1, 2] ; Barros-Filho, Mateus Camargo [1] ; Marchi, Fabio Albuquerque [1] ; Custodio Domingues, Maria Aparecida [3] ; de Carvalho, Genival Barbosa [4] ; Drigo, Sandra Aparecida [5] ; Kowalski, Luiz Paulo [4] ; Rogatto, Silvia Regina [5, 6]
Total Authors: 8
[1] CIPE AC Camargo Canc Ctr, Int Res Ctr, Sao Paulo - Brazil
[2] Sao Paulo State Univ UNESP, Dept Genet, Inst Biosci, Botucatu, SP - Brazil
[3] Sao Paulo State Univ UNESP, Dept Pathol, Fac Med, Botucatu, SP - Brazil
[4] AC Camargo Canc Ctr, Dept Head & Neck Surg & Otorhinolaryngol, Sao Paulo - Brazil
[5] Sao Paulo State Univ UNESP, Dept Surg & Orthoped, Fac Med, Botucatu, SP - Brazil
[6] Univ Southern Denmark, Dept Clin Genet, Vejle Hosp, Inst Reg Hlth Res, Vejle - Denmark
Total Affiliations: 6
Document type: Journal article
Source: Oral Oncology; v. 93, p. 76-84, JUN 2019.
Web of Science Citations: 1

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. (AU)

FAPESP's process: 08/57887-9 - National Institute of Oncogenomics
Grantee:Luiz Paulo Kowalski
Support type: Research Projects - Thematic Grants