PMID- 38425711 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20240302 IS - 2162-2531 (Print) IS - 2162-2531 (Electronic) IS - 2162-2531 (Linking) VI - 35 IP - 1 DP - 2024 Mar 12 TI - MiR-449a antagonizes EMT through IL-6-mediated trans-signaling in laryngeal squamous cancer. PG - 102140 LID - 10.1016/j.omtn.2024.102140 [doi] LID - 102140 AB - 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. CI - (c) 2024 The Author(s). FAU - Cossu, Alessia Maria AU - Cossu AM AD - Department of Precision Medicine, University of Campania "Luigi Vanvitelli", 80138 Naples, Italy. AD - Biogem Scarl, Institute of Genetic Research, 83031 Ariano Irpino, Italy. FAU - Melisi, Federica AU - Melisi F AD - Department of Precision Medicine, University of Campania "Luigi Vanvitelli", 80138 Naples, Italy. AD - Biogem Scarl, Institute of Genetic Research, 83031 Ariano Irpino, Italy. FAU - Noviello, Teresa Maria Rosaria AU - Noviello TMR AD - Biogem Scarl, Institute of Genetic Research, 83031 Ariano Irpino, Italy. AD - Department of Electrical Engineering and Information Technology, University of Naples "Federico II", Napoli, Italy. FAU - Pasquale, Lucia Stefania AU - Pasquale LS AD - Department of Precision Medicine, University of Campania "Luigi Vanvitelli", 80138 Naples, Italy. AD - Biogem Scarl, Institute of Genetic Research, 83031 Ariano Irpino, Italy. FAU - Grisolia, Piera AU - Grisolia P AD - Department of Precision Medicine, University of Campania "Luigi Vanvitelli", 80138 Naples, Italy. AD - Biogem Scarl, Institute of Genetic Research, 83031 Ariano Irpino, Italy. FAU - Reale, Carla AU - Reale C AD - Biogem Scarl, Institute of Genetic Research, 83031 Ariano Irpino, Italy. FAU - Bocchetti, Marco AU - Bocchetti M AD - Department of Precision Medicine, University of Campania "Luigi Vanvitelli", 80138 Naples, Italy. AD - Biogem Scarl, Institute of Genetic Research, 83031 Ariano Irpino, Italy. FAU - Falco, Michela AU - Falco M AD - Biogem Scarl, Institute of Genetic Research, 83031 Ariano Irpino, Italy. FAU - Tammaro, Chiara AU - Tammaro C AD - Biogem Scarl, Institute of Genetic Research, 83031 Ariano Irpino, Italy. FAU - Accardo, Nunzio AU - Accardo N AD - Ear, Nose, and Throat Unit, AORN "Antonio Cardarelli", Naples, Italy. FAU - Longo, Francesco AU - Longo F AD - Head and Neck Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori, "Fondazione G. Pascale", IRCCS, Naples, Italy. FAU - Allosso, Salvatore AU - Allosso S AD - Department of Neurosciences, Reproductive and Odontostomatological Sciences, UOC Federico II, 80121 Naples, Italy. FAU - Mesolella, Massimo AU - Mesolella M AD - Department of Neurosciences, Reproductive and Odontostomatological Sciences, UOC Federico II, 80121 Naples, Italy. FAU - Addeo, Raffaele AU - Addeo R AD - Medical Oncology Unit, San Giovanni di Dio Hospital, 80027 Frattamaggiore, Italy. FAU - Perri, Francesco AU - Perri F AD - Head and Neck Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori, "Fondazione G. Pascale", IRCCS, Naples, Italy. FAU - Ottaiano, Alessandro AU - Ottaiano A AD - SSD Innovative Therapies for Abdominal Metastases, Abdominal Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori, "Fondazione G. Pascale", IRCCS, Naples, Italy. FAU - Ricciardiello, Filippo AU - Ricciardiello F AD - Ear, Nose, and Throat Unit, AORN "Antonio Cardarelli", Naples, Italy. FAU - Amler, Evzen AU - Amler E AD - UCEEB, Czech Technical University, Trinecka 1024, 273 43 Bustehrad, Czech. FAU - Ambrosino, Concetta AU - Ambrosino C AD - Biogem Scarl, Institute of Genetic Research, 83031 Ariano Irpino, Italy. AD - Department of Science and Technology, University of Sannio, 82100 Benevento, Italy. FAU - Misso, Gabriella AU - Misso G AD - Department of Precision Medicine, University of Campania "Luigi Vanvitelli", 80138 Naples, Italy. FAU - Ceccarelli, Michele AU - Ceccarelli M AD - Biogem Scarl, Institute of Genetic Research, 83031 Ariano Irpino, Italy. AD - Department of Electrical Engineering and Information Technology, University of Naples "Federico II", Napoli, Italy. FAU - Caraglia, Michele AU - Caraglia M AD - Department of Precision Medicine, University of Campania "Luigi Vanvitelli", 80138 Naples, Italy. AD - Biogem Scarl, Institute of Genetic Research, 83031 Ariano Irpino, Italy. FAU - Scrima, Marianna AU - Scrima M AD - Biogem Scarl, Institute of Genetic Research, 83031 Ariano Irpino, Italy. LA - eng PT - Journal Article DEP - 20240206 PL - United States TA - Mol Ther Nucleic Acids JT - Molecular therapy. Nucleic acids JID - 101581621 PMC - PMC10901858 OTO - NOTNLM OT - IL-6 trans-signaling OT - LSCC OT - MT: non-coding RNAs OT - gene expression OT - metastases miR-449a OT - microRNAs COIS- The all authors declare that they have no conflicts of interests. EDAT- 2024/03/01 06:44 MHDA- 2024/03/01 06:45 PMCR- 2024/02/06 CRDT- 2024/03/01 03:51 PHST- 2023/08/30 00:00 [received] PHST- 2024/02/01 00:00 [accepted] PHST- 2024/03/01 06:45 [medline] PHST- 2024/03/01 06:44 [pubmed] PHST- 2024/03/01 03:51 [entrez] PHST- 2024/02/06 00:00 [pmc-release] AID - S2162-2531(24)00027-1 [pii] AID - 102140 [pii] AID - 10.1016/j.omtn.2024.102140 [doi] PST - epublish SO - Mol Ther Nucleic Acids. 2024 Feb 6;35(1):102140. doi: 10.1016/j.omtn.2024.102140. eCollection 2024 Mar 12.