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The ability of RSV to provide beneficial effects for neurological, cardiovascular, and cancer disorders rekindled the interest to explore the molecular mechanisms behind its pleiotropic effects, which are due to the modulation of coding and noncoding genes involved in many key biological pathways. With a computational approach, including docking studies and thermodynamics calculations followed by 200\u2010ns\u2010long molecular dynamics and a clustering analysis, we hypothesized the stabilizing binding between RSV and G4 structures of telomeric repeat\u2010containing RNA (TERRA), which is a tumor\u2010suppressive long noncoding RNAs (lncRNA) involved in the regulation of telomere maintenance. In vitro studies performed on cellular models of multiple myeloma (MM) strengthened our hypothesis by highlighting that the antiproliferative and apoptotic effect induced by the treatment with RSV is associated with an increase of TERRA transcript and with upregulation of telomeric heterochromatin markers, such as H3K27Me3 and H4K20Me3, and of the hallmark of apoptosis, cleaved\u2010poly(ADP\u2010ribose) polymerase\u20101. Our results propose innovative insights underlying the multifaceted role of RSV in MM, by pointing out the role of this natural compound in an lncRNA\u2010mediated regulation to counteract cellular immortality.<\/jats:p>","DOI":"10.1002\/ardp.202400269","type":"journal-article","created":{"date-parts":[[2024,6,22]],"date-time":"2024-06-22T12:55:15Z","timestamp":1719060915000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["TERRA G\u2010quadruplex stabilization behind the anti\u2010multiple myeloma activity: Novel insights about resveratrol pleiotropic effects"],"prefix":"10.1002","volume":"357","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0680-7097","authenticated-orcid":false,"given":"Roberta","family":"Rocca","sequence":"first","affiliation":[{"name":"Net4Science srl University Magna Gr\u00e6cia Catanzaro Italy"},{"name":"Associazione CRISEA\u2010Centro di Ricerca e Servizi Avanzati per l'Innovazione 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