Definition of miRNA Signatures of Nodal Metastasis in LCa: miR-449a Targets Notch Genes and Suppresses Cell Migration and Invasion
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 therape...
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| Format: | Article |
| Language: | English |
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Elsevier
2020-06-01
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| Series: | Molecular Therapy: Nucleic Acids |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2162253120301141 |
| _version_ | 1819289697504985088 |
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| author | Hiromichi Kawasaki Takashi Takeuchi Filippo Ricciardiello Angela Lombardi Elia Biganzoli Marco Fornili Davide De Bortoli Massimo Mesolella Alessia Maria Cossu Marianna Scrima Rosanna Capasso Michela Falco Giovanni Motta Gaetano Motta Domenico Testa Stefania De Luca Flavia Oliva Teresa Abate Salvatore Mazzone Gabriella Misso Michele Caraglia |
| author_facet | Hiromichi Kawasaki Takashi Takeuchi Filippo Ricciardiello Angela Lombardi Elia Biganzoli Marco Fornili Davide De Bortoli Massimo Mesolella Alessia Maria Cossu Marianna Scrima Rosanna Capasso Michela Falco Giovanni Motta Gaetano Motta Domenico Testa Stefania De Luca Flavia Oliva Teresa Abate Salvatore Mazzone Gabriella Misso Michele Caraglia |
| author_sort | Hiromichi Kawasaki |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-24T03:10:58Z |
| format | Article |
| id | doaj.art-846c744f593a40159c688d38225c6a45 |
| institution | Directory Open Access Journal |
| issn | 2162-2531 |
| language | English |
| last_indexed | 2024-12-24T03:10:58Z |
| publishDate | 2020-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Nucleic Acids |
| spelling | doaj.art-846c744f593a40159c688d38225c6a452022-12-21T17:17:49ZengElsevierMolecular Therapy: Nucleic Acids2162-25312020-06-0120711724Definition of miRNA Signatures of Nodal Metastasis in LCa: miR-449a Targets Notch Genes and Suppresses Cell Migration and InvasionHiromichi Kawasaki0Takashi Takeuchi1Filippo Ricciardiello2Angela Lombardi3Elia Biganzoli4Marco Fornili5Davide De Bortoli6Massimo Mesolella7Alessia Maria Cossu8Marianna Scrima9Rosanna Capasso10Michela Falco11Giovanni Motta12Gaetano Motta13Domenico Testa14Stefania De Luca15Flavia Oliva16Teresa Abate17Salvatore Mazzone18Gabriella Misso19Michele Caraglia20Department of Precision Medicine, University of Campania “Luigi Vanvitelli,” Naples, Italy; Drug Discovery Laboratory, Wakunaga Pharmaceutical, Hiroshima, JapanDepartment of Precision Medicine, University of Campania “Luigi Vanvitelli,” Naples, Italy; Molecular Diagnostics Division, Wakunaga Pharmaceutical, Hiroshima, JapanEar, Nose, and Throat Unit, AORN “Antonio Cardarelli,” Naples, ItalyDepartment of Precision Medicine, University of Campania “Luigi Vanvitelli,” Naples, ItalyUnit 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, ItalyUnit 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, ItalyUnit 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, ItalyEar, Nose, and Throat Unit, AORN “Antonio Cardarelli,” Naples, ItalyIRGS, Biogem, Molecular Oncology and Precision Medicine Laboratory, Via Camporeale, 83031 Ariano Irpino, ItalyIRGS, Biogem, Molecular Oncology and Precision Medicine Laboratory, Via Camporeale, 83031 Ariano Irpino, ItalyDepartment of Precision Medicine, University of Campania “Luigi Vanvitelli,” Naples, ItalyDepartment of Precision Medicine, University of Campania “Luigi Vanvitelli,” Naples, ItalyDepartment of Precision Medicine, University of Campania “Luigi Vanvitelli,” Naples, ItalyDepartment of Mental and Physical Health and Preventive Medicine, University of Campania “Luigi Vanvitelli,” Naples, ItalyDepartment of Mental and Physical Health and Preventive Medicine, University of Campania “Luigi Vanvitelli,” Naples, ItalyDepartment of Mental and Physical Health and Preventive Medicine, University of Campania “Luigi Vanvitelli,” Naples, ItalyEar, Nose, and Throat Unit, AORN “Antonio Cardarelli,” Naples, ItalyEar, Nose, and Throat Unit, AORN “Antonio Cardarelli,” Naples, ItalyEar, Nose, and Throat Unit, AORN “Antonio Cardarelli,” Naples, ItalyDepartment of Precision Medicine, University of Campania “Luigi Vanvitelli,” Naples, Italy; Corresponding author: Gabriella Misso, Department of Precision Medicine, University of Campania “Luigi Vanvitelli,” Naples, Italy.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; Corresponding author: Michele Caraglia, Department of Precision Medicine, University of Campania “Luigi Vanvitelli,” Naples, Italy.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.http://www.sciencedirect.com/science/article/pii/S2162253120301141microRNAlaryngeal cancermetastasesmiR-449amiR-133bmigration |
| spellingShingle | Hiromichi Kawasaki Takashi Takeuchi Filippo Ricciardiello Angela Lombardi Elia Biganzoli Marco Fornili Davide De Bortoli Massimo Mesolella Alessia Maria Cossu Marianna Scrima Rosanna Capasso Michela Falco Giovanni Motta Gaetano Motta Domenico Testa Stefania De Luca Flavia Oliva Teresa Abate Salvatore Mazzone Gabriella Misso Michele Caraglia Definition of miRNA Signatures of Nodal Metastasis in LCa: miR-449a Targets Notch Genes and Suppresses Cell Migration and Invasion Molecular Therapy: Nucleic Acids microRNA laryngeal cancer metastases miR-449a miR-133b migration |
| title | Definition of miRNA Signatures of Nodal Metastasis in LCa: miR-449a Targets Notch Genes and Suppresses Cell Migration and Invasion |
| title_full | Definition of miRNA Signatures of Nodal Metastasis in LCa: miR-449a Targets Notch Genes and Suppresses Cell Migration and Invasion |
| title_fullStr | Definition of miRNA Signatures of Nodal Metastasis in LCa: miR-449a Targets Notch Genes and Suppresses Cell Migration and Invasion |
| title_full_unstemmed | Definition of miRNA Signatures of Nodal Metastasis in LCa: miR-449a Targets Notch Genes and Suppresses Cell Migration and Invasion |
| title_short | Definition of miRNA Signatures of Nodal Metastasis in LCa: miR-449a Targets Notch Genes and Suppresses Cell Migration and Invasion |
| title_sort | definition of mirna signatures of nodal metastasis in lca mir 449a targets notch genes and suppresses cell migration and invasion |
| topic | microRNA laryngeal cancer metastases miR-449a miR-133b migration |
| url | http://www.sciencedirect.com/science/article/pii/S2162253120301141 |
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