PMID- 33297397 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20201226 IS - 2072-6694 (Print) IS - 2072-6694 (Electronic) IS - 2072-6694 (Linking) VI - 12 IP - 12 DP - 2020 Dec 7 TI - Mi-RNA-888-5p Is Involved in S-Adenosylmethionine Antitumor Effects in Laryngeal Squamous Cancer Cells. LID - 10.3390/cancers12123665 [doi] LID - 3665 AB - (1) Purpose: The methyl donor S-Adenosylmethionine (AdoMet) has been widely explored as a therapeutic compound, and its application-alone or in combination with other molecules-is emerging as a potential effective strategy for the treatment and chemoprevention of tumours. In this study, we investigated the antitumor activity of AdoMet in Laryngeal Squamous Cell Carcinoma (LSCC), exploring the underlying mechanisms. (2) Results: We demonstrated that AdoMet induced ROS generation and triggered autophagy with a consistent increase in LC3B-II autophagy-marker in JHU-SCC-011 and HNO210 LSCC cells. AdoMet induced ER-stress and activated UPR signaling through the upregulation of the spliced form of XBP1 and CHOP. To gain new insights into the molecular mechanisms underlying the antitumor activity of AdoMet, we evaluated the regulation of miRNA expression profile and we found a downregulation of miR-888-5p. We transfected LSCC cells with miR-888-5p inhibitor and exposed the cells to AdoMet for 48 and 72 h. The combination of AdoMet with miR-888-5p inhibitor synergistically induced both apoptosis and inhibited cell migration paralleled by the up-regulation of MYCBP and CDH1 genes and of their targets. (3) Conclusion: Overall, these data highlighted that epigenetic reprogramming of miRNAs by AdoMet play an important role in inhibiting apoptosis and migration in LSCC cell lines. FAU - Pagano, Martina AU - Pagano M AD - Department of Precision Medicine, University of Campania "Luigi Vanvitelli", Via L. De Crecchio 7, 80138 Naples, Italy. FAU - Mosca, Laura AU - Mosca L AD - Department of Precision Medicine, University of Campania "Luigi Vanvitelli", Via L. De Crecchio 7, 80138 Naples, Italy. FAU - Vitiello, Francesca AU - Vitiello F AD - Department of Precision Medicine, University of Campania "Luigi Vanvitelli", Via L. De Crecchio 7, 80138 Naples, Italy. FAU - Ilisso, Concetta Paola AU - Ilisso CP AD - Department of Precision Medicine, University of Campania "Luigi Vanvitelli", Via L. De Crecchio 7, 80138 Naples, Italy. FAU - Coppola, Alessandra AU - Coppola A AD - Department of Precision Medicine, University of Campania "Luigi Vanvitelli", Via L. De Crecchio 7, 80138 Naples, Italy. FAU - Borzacchiello, Luigi AU - Borzacchiello L AD - Department of Precision Medicine, University of Campania "Luigi Vanvitelli", Via L. De Crecchio 7, 80138 Naples, Italy. FAU - Mele, Luigi AU - Mele L AD - Department of Experimental Medicine, University of Campania "Luigi Vanvitelli", 80138 Naples, Italy. FAU - Caruso, Francesca Pia AU - Caruso FP AUID- ORCID: 0000-0002-2206-1459 AD - Department of Electrical Engineering and Information Technology (DIETI), University of Naples "Federico II", 80128 Naples, Italy. AD - Bioinformatics Lab, BIOGEM, 83031 Ariano Irpino, Italy. FAU - Ceccarelli, Michele AU - Ceccarelli M AD - Department of Electrical Engineering and Information Technology (DIETI), University of Naples "Federico II", 80128 Naples, Italy. AD - Bioinformatics Lab, BIOGEM, 83031 Ariano Irpino, Italy. FAU - Caraglia, Michele AU - Caraglia M AUID- ORCID: 0000-0003-2408-6091 AD - Department of Precision Medicine, University of Campania "Luigi Vanvitelli", Via L. De Crecchio 7, 80138 Naples, Italy. AD - Laboratory of Precision and Molecular Oncology, BIOGEM, 83031 Ariano Irpino, Italy. FAU - Cacciapuoti, Giovanna AU - Cacciapuoti G AD - Department of Precision Medicine, University of Campania "Luigi Vanvitelli", Via L. De Crecchio 7, 80138 Naples, Italy. FAU - Porcelli, Marina AU - Porcelli M AUID- ORCID: 0000-0003-0192-1728 AD - Department of Precision Medicine, University of Campania "Luigi Vanvitelli", Via L. De Crecchio 7, 80138 Naples, Italy. LA - eng PT - Journal Article DEP - 20201207 PL - Switzerland TA - Cancers (Basel) JT - Cancers JID - 101526829 PMC - PMC7762311 OTO - NOTNLM OT - ER-stress OT - S-Adenosylmethionine OT - apoptosis OT - autophagy OT - laryngeal squamous cancer cells OT - miR-888 OT - microRNA regulation COIS- The authors declare no competing interests. EDAT- 2020/12/11 06:00 MHDA- 2020/12/11 06:01 PMCR- 2020/12/07 CRDT- 2020/12/10 01:03 PHST- 2020/11/19 00:00 [received] PHST- 2020/12/02 00:00 [accepted] PHST- 2020/12/10 01:03 [entrez] PHST- 2020/12/11 06:00 [pubmed] PHST- 2020/12/11 06:01 [medline] PHST- 2020/12/07 00:00 [pmc-release] AID - cancers12123665 [pii] AID - cancers-12-03665 [pii] AID - 10.3390/cancers12123665 [doi] PST - epublish SO - Cancers (Basel). 2020 Dec 7;12(12):3665. doi: 10.3390/cancers12123665.