PMID- 31109699
OWN - NLM
STAT- MEDLINE
DCOM- 20200504
LR  - 20200505
IS  - 1879-0593 (Electronic)
IS  - 1368-8375 (Linking)
VI  - 93
DP  - 2019 Jun
TI  - Integrated miRNA and mRNA expression analysis uncovers drug targets in laryngeal 
      squamous cell carcinoma patients.
PG  - 76-84
LID - S1368-8375(19)30129-0 [pii]
LID - 10.1016/j.oraloncology.2019.04.018 [doi]
AB  - 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.
CI  - Copyright (c) 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.
FAU - Lapa, Rainer Marco Lopez
AU  - Lapa RML
AD  - International Research Center, CIPE - A.C.Camargo Cancer Center, Sao Paulo, 
      Brazil; Department of Genetics, Institute of Bioscience, Sao Paulo State 
      University - UNESP, Botucatu, SP, Brazil.
FAU - Barros-Filho, Mateus Camargo
AU  - Barros-Filho MC
AD  - International Research Center, CIPE - A.C.Camargo Cancer Center, Sao Paulo, 
      Brazil.
FAU - Marchi, Fabio Albuquerque
AU  - Marchi FA
AD  - International Research Center, CIPE - A.C.Camargo Cancer Center, Sao Paulo, 
      Brazil.
FAU - Domingues, Maria Aparecida Custodio
AU  - Domingues MAC
AD  - Department of Pathology, Faculty of Medicine, Sao Paulo State University-UNESP, 
      Botucatu, SP, Brazil.
FAU - de Carvalho, Genival Barbosa
AU  - de Carvalho GB
AD  - Department of Head and Neck Surgery and Otorhinolaryngology, A.C.Camargo Cancer 
      Center, Sao Paulo Brazil.
FAU - Drigo, Sandra Aparecida
AU  - Drigo SA
AD  - Department of Surgery and Orthopedics, Faculty of Medicine, Sao Paulo State 
      University - UNESP, Botucatu, SP, Brazil.
FAU - Kowalski, Luiz Paulo
AU  - Kowalski LP
AD  - Department of Head and Neck Surgery and Otorhinolaryngology, A.C.Camargo Cancer 
      Center, Sao Paulo Brazil.
FAU - Rogatto, Silvia Regina
AU  - Rogatto SR
AD  - Department of Surgery and Orthopedics, Faculty of Medicine, Sao Paulo State 
      University - UNESP, Botucatu, SP, Brazil; Department of Clinical Genetics, Vejle 
      Hospital, Institute of Regional Health Research, University of Southern Denmark, 
      Denmark. Electronic address: silvia.regina.rogatto@rsyd.dk.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190429
PL  - England
TA  - Oral Oncol
JT  - Oral oncology
JID - 9709118
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (MicroRNAs)
RN  - 0 (RNA, Messenger)
SB  - IM
MH  - Biomarkers, Tumor/genetics
MH  - Carcinoma, Squamous Cell/*genetics
MH  - Down-Regulation
MH  - Female
MH  - Gene Expression Profiling/*methods
MH  - Gene Expression Regulation, Neoplastic
MH  - Gene Regulatory Networks
MH  - Humans
MH  - Laryngeal Neoplasms/*genetics
MH  - Male
MH  - MicroRNAs/*genetics
MH  - Molecular Targeted Therapy
MH  - RNA, Messenger/*genetics
MH  - Survival Analysis
OTO - NOTNLM
OT  - Chemotherapy
OT  - Drug targets
OT  - Integrative analysis
OT  - Laryngeal squamous cell carcinoma
OT  - Treatment
OT  - mRNA
OT  - miRNAs
EDAT- 2019/05/22 06:00
MHDA- 2020/05/06 06:00
CRDT- 2019/05/22 06:00
PHST- 2019/01/08 00:00 [received]
PHST- 2019/03/20 00:00 [revised]
PHST- 2019/04/24 00:00 [accepted]
PHST- 2019/05/22 06:00 [entrez]
PHST- 2019/05/22 06:00 [pubmed]
PHST- 2020/05/06 06:00 [medline]
AID - S1368-8375(19)30129-0 [pii]
AID - 10.1016/j.oraloncology.2019.04.018 [doi]
PST - ppublish
SO  - Oral Oncol. 2019 Jun;93:76-84. doi: 10.1016/j.oraloncology.2019.04.018. Epub 2019 
      Apr 29.