Molecular Therapy: Nucleic Acids (Mar 2024)
MiR-449a antagonizes EMT through IL-6-mediated trans-signaling in laryngeal squamous cancer
- Alessia Maria Cossu,
- Federica Melisi,
- Teresa Maria Rosaria Noviello,
- Lucia Stefania Pasquale,
- Piera Grisolia,
- Carla Reale,
- Marco Bocchetti,
- Michela Falco,
- Chiara Tammaro,
- Nunzio Accardo,
- Francesco Longo,
- Salvatore Allosso,
- Massimo Mesolella,
- Raffaele Addeo,
- Francesco Perri,
- Alessandro Ottaiano,
- Filippo Ricciardiello,
- Evzen Amler,
- Concetta Ambrosino,
- Gabriella Misso,
- Michele Ceccarelli,
- Michele Caraglia,
- Marianna Scrima
Affiliations
- Alessia Maria Cossu
- Department of Precision Medicine, University of Campania ''Luigi Vanvitelli'', 80138 Naples, Italy; Biogem Scarl, Institute of Genetic Research, 83031 Ariano Irpino, Italy; Corresponding author: Alessia Maria Cossu, Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy.
- Federica Melisi
- Department of Precision Medicine, University of Campania ''Luigi Vanvitelli'', 80138 Naples, Italy; Biogem Scarl, Institute of Genetic Research, 83031 Ariano Irpino, Italy
- Teresa Maria Rosaria Noviello
- Biogem Scarl, Institute of Genetic Research, 83031 Ariano Irpino, Italy; Department of Electrical Engineering and Information Technology, University of Naples ''Federico II'', Napoli, Italy
- Lucia Stefania Pasquale
- Department of Precision Medicine, University of Campania ''Luigi Vanvitelli'', 80138 Naples, Italy; Biogem Scarl, Institute of Genetic Research, 83031 Ariano Irpino, Italy
- Piera Grisolia
- Department of Precision Medicine, University of Campania ''Luigi Vanvitelli'', 80138 Naples, Italy; Biogem Scarl, Institute of Genetic Research, 83031 Ariano Irpino, Italy
- Carla Reale
- Biogem Scarl, Institute of Genetic Research, 83031 Ariano Irpino, Italy
- Marco Bocchetti
- Department of Precision Medicine, University of Campania ''Luigi Vanvitelli'', 80138 Naples, Italy; Biogem Scarl, Institute of Genetic Research, 83031 Ariano Irpino, Italy
- Michela Falco
- Biogem Scarl, Institute of Genetic Research, 83031 Ariano Irpino, Italy
- Chiara Tammaro
- Biogem Scarl, Institute of Genetic Research, 83031 Ariano Irpino, Italy
- Nunzio Accardo
- Ear, Nose, and Throat Unit, AORN ''Antonio Cardarelli'', Naples, Italy
- Francesco Longo
- Head and Neck Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori, ''Fondazione G. Pascale'', IRCCS, Naples, Italy
- Salvatore Allosso
- Department of Neurosciences, Reproductive and Odontostomatological Sciences, UOC Federico II, 80121 Naples, Italy
- Massimo Mesolella
- Department of Neurosciences, Reproductive and Odontostomatological Sciences, UOC Federico II, 80121 Naples, Italy
- Raffaele Addeo
- Medical Oncology Unit, San Giovanni di Dio Hospital, 80027 Frattamaggiore, Italy
- Francesco Perri
- Head and Neck Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori, ''Fondazione G. Pascale'', IRCCS, Naples, Italy
- Alessandro Ottaiano
- SSD Innovative Therapies for Abdominal Metastases, Abdominal Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori, ''Fondazione G. Pascale'', IRCCS, Naples, Italy
- Filippo Ricciardiello
- Ear, Nose, and Throat Unit, AORN ''Antonio Cardarelli'', Naples, Italy
- Evzen Amler
- UCEEB, Czech Technical University, Třinecká 1024, 273 43 Buštěhrad, Czech
- Concetta Ambrosino
- Biogem Scarl, Institute of Genetic Research, 83031 Ariano Irpino, Italy; Department of Science and Technology, University of Sannio, 82100 Benevento, Italy
- Gabriella Misso
- Department of Precision Medicine, University of Campania ''Luigi Vanvitelli'', 80138 Naples, Italy
- Michele Ceccarelli
- Biogem Scarl, Institute of Genetic Research, 83031 Ariano Irpino, Italy; Department of Electrical Engineering and Information Technology, University of Naples ''Federico II'', Napoli, Italy
- Michele Caraglia
- Department of Precision Medicine, University of Campania ''Luigi Vanvitelli'', 80138 Naples, Italy; Biogem Scarl, Institute of Genetic Research, 83031 Ariano Irpino, Italy
- Marianna Scrima
- Biogem Scarl, Institute of Genetic Research, 83031 Ariano Irpino, Italy; Corresponding author: Marianna Scrima, Biogem Scarl, Institute of Genetic Research, 83031 Ariano Irpino, Italy.
- Journal volume & issue
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Vol. 35,
no. 1
p. 102140
Abstract
MicroRNAs (miRNAs) are involved in post-transcriptional gene expression regulation and in mechanisms of cancer growth and metastases. In this light, miRNAs could be promising therapeutic targets and biomarkers in clinical practice. Therefore, we investigated if specific miRNAs and their target genes contribute to laryngeal squamous cell carcinoma (LSCC) development. We found a significant decrease of miR-449a in LSCC patients with nodal metastases (63.3%) compared with patients without nodal involvement (44%). The AmpliSeq Transcriptome of HNO-210 miR-449a-transfected cell lines allowed the identification of IL6-R as a potential target. Moreover, the downregulation of IL6-R and the phosphorylation reduction of the downstream signaling effectors, suggested the inhibition of the IL-6 trans-signaling pathway. These biochemical effects were paralleled by a significant inhibition of invasion and migration in vitro and in vivo, supporting an involvement of epithelial-mesenchymal transition. These findings indicate that miR-449a contributes to suppress the metastasization of LSCC by the IL-6 trans-signaling block and affects sensitivity to external stimuli that mimic pro-inflammatory conditions.
