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.

Biogem Scarl Institute of Genetic Research 83031 Ariano Irpino Italy

Department of Electrical Engineering and Information Technology University of Naples Federico 2 Napoli Italy

Department of Neurosciences Reproductive and Odontostomatological Sciences UOC Federico 2 80121 Naples Italy

Department of Precision Medicine University of Campania Luigi Vanvitelli 80138 Naples Italy

Department of Science and Technology University of Sannio 82100 Benevento Italy

Ear Nose and Throat Unit AORN Antonio Cardarelli Naples Italy

Head and Neck Unit Istituto Nazionale per lo Studio e la Cura dei Tumori Fondazione G Pascale IRCCS Naples Italy

Medical Oncology Unit San Giovanni di Dio Hospital 80027 Frattamaggiore Italy

SSD Innovative Therapies for Abdominal Metastases Abdominal Oncology Istituto Nazionale per lo Studio e la Cura dei Tumori Fondazione G Pascale IRCCS Naples Italy

UCEEB Czech Technical University Třinecká 1024 273 43 Buštěhrad Czech

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