Definition of miRNA Signatures of Nodal Metastasis in LCa: miR-449a Targets Notch Genes and Suppresses Cell Migration and Invasion.

Notch1 Notch2 invasion laryngeal cancer lymph nodes metastases miR-133b miR-449a microRNA migration

Journal

Molecular therapy. Nucleic acids
ISSN: 2162-2531
Titre abrégé: Mol Ther Nucleic Acids
Pays: United States
ID NLM: 101581621

Informations de publication

Date de publication:
05 Jun 2020
Historique:
received: 04 02 2020
revised: 08 04 2020
accepted: 17 04 2020
pubmed: 14 5 2020
medline: 14 5 2020
entrez: 14 5 2020
Statut: ppublish

Résumé

Laryngeal cancer (LCa), a neoplasm of the head and neck region, is a leading cause of death worldwide. Surgical intervention remains the mainstay of LCa treatment, but a crucial point is represented by the possible nodal involvement. Therefore, it is urgently needed to develop biomarkers and therapeutic tools able to drive treatment approaches for LCa. In this study, we investigated deregulated microRNAs (miRNAs) in tissues from LCa patients with either lymph node metastases (N+) or not (N-). miRNA expression profiling was performed by a comprehensive PCR array and subsequent validation by RT-qPCR. Results showed a significant decrease of miR-449a expression in N+ compared to N- patients, and miR-133b down-modulation in LCa tissues compared to paired normal ones. Receiver operating characteristic (ROC) curve analysis revealed the potential diagnostic power of miR-133b for LCa detection. According to the validation results, we selected miR-449a for further in vitro studies. Ectopic miR-449a expression in the LCa cell line Hep-2 inhibited invasion and motility in vitro, slowed cell proliferation, and induced the downregulation of Notch1 and Notch2 as direct targets of miR-449a. Collectively, this study provides new promising biomarkers for LCa diagnosis and a new opportunity to use miR-449a for the treatment of nodal metastases in LCa patients.

Identifiants

pubmed: 32402942
pii: S2162-2531(20)30114-1
doi: 10.1016/j.omtn.2020.04.006
pmc: PMC7218231
pii:
doi:

Types de publication

Journal Article

Langues

eng

Pagination

711-724

Informations de copyright

Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.

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Auteurs

Hiromichi Kawasaki (H)

Department of Precision Medicine, University of Campania "Luigi Vanvitelli," Naples, Italy; Drug Discovery Laboratory, Wakunaga Pharmaceutical, Hiroshima, Japan.

Takashi Takeuchi (T)

Department of Precision Medicine, University of Campania "Luigi Vanvitelli," Naples, Italy; Molecular Diagnostics Division, Wakunaga Pharmaceutical, Hiroshima, Japan.

Filippo Ricciardiello (F)

Ear, Nose, and Throat Unit, AORN "Antonio Cardarelli," Naples, Italy.

Angela Lombardi (A)

Department of Precision Medicine, University of Campania "Luigi Vanvitelli," Naples, Italy.

Elia Biganzoli (E)

Unit of Medical Statistics, Biometry and Bioinformatics "Giulio A. Maccacaro," Department of Clinical Sciences and Community Health & DSRC, University of Milan Campus Cascina Rosa, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.

Marco Fornili (M)

Unit of Medical Statistics, Biometry and Bioinformatics "Giulio A. Maccacaro," Department of Clinical Sciences and Community Health & DSRC, University of Milan Campus Cascina Rosa, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.

Davide De Bortoli (D)

Unit of Medical Statistics, Biometry and Bioinformatics "Giulio A. Maccacaro," Department of Clinical Sciences and Community Health & DSRC, University of Milan Campus Cascina Rosa, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.

Massimo Mesolella (M)

Ear, Nose, and Throat Unit, AORN "Antonio Cardarelli," Naples, Italy.

Alessia Maria Cossu (AM)

IRGS, Biogem, Molecular Oncology and Precision Medicine Laboratory, Via Camporeale, 83031 Ariano Irpino, Italy.

Marianna Scrima (M)

IRGS, Biogem, Molecular Oncology and Precision Medicine Laboratory, Via Camporeale, 83031 Ariano Irpino, Italy.

Rosanna Capasso (R)

Department of Precision Medicine, University of Campania "Luigi Vanvitelli," Naples, Italy.

Michela Falco (M)

Department of Precision Medicine, University of Campania "Luigi Vanvitelli," Naples, Italy.

Giovanni Motta (G)

Department of Precision Medicine, University of Campania "Luigi Vanvitelli," Naples, Italy.

Gaetano Motta (G)

Department of Mental and Physical Health and Preventive Medicine, University of Campania "Luigi Vanvitelli," Naples, Italy.

Domenico Testa (D)

Department of Mental and Physical Health and Preventive Medicine, University of Campania "Luigi Vanvitelli," Naples, Italy.

Stefania De Luca (S)

Department of Mental and Physical Health and Preventive Medicine, University of Campania "Luigi Vanvitelli," Naples, Italy.

Flavia Oliva (F)

Ear, Nose, and Throat Unit, AORN "Antonio Cardarelli," Naples, Italy.

Teresa Abate (T)

Ear, Nose, and Throat Unit, AORN "Antonio Cardarelli," Naples, Italy.

Salvatore Mazzone (S)

Ear, Nose, and Throat Unit, AORN "Antonio Cardarelli," Naples, Italy.

Gabriella Misso (G)

Department of Precision Medicine, University of Campania "Luigi Vanvitelli," Naples, Italy. Electronic address: gabriella.misso@unicampania.it.

Michele Caraglia (M)

Department of Precision Medicine, University of Campania "Luigi Vanvitelli," Naples, Italy; IRGS, Biogem, Molecular Oncology and Precision Medicine Laboratory, Via Camporeale, 83031 Ariano Irpino, Italy. Electronic address: michele.caraglia@unicampania.it.

Classifications MeSH