{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T16:24:24Z","timestamp":1792686264275,"version":"4.5.0"},"reference-count":39,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,7,20]],"date-time":"2025-07-20T00:00:00Z","timestamp":1752969600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["PNRR\u2010MAD\u20102022\u201012376707"],"award-info":[{"award-number":["PNRR\u2010MAD\u20102022\u201012376707"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Diffuse large B\u2010cell lymphoma (DLBCL) is a heterogeneous disorder. Prognostic factors include genomic alterations and cell\u2010of\u2010origin (COO) subtypes, even though they cannot fully predict treatment response. MicroRNAs (miRNAs) deregulated in patient tumours and blood are promising non\u2010invasive biomarkers. Several circulating miRNAs were found to be correlated with progression\u2010free survival (PFS), independently of other prognosticators. However, miRNA signatures, rather than individual miRNAs, represent more reliable biomarkers and a better mirror of the disease. In this study, we identified circulating miRNAs differentially expressed between R\u2010CHOP refractory and responding subjects by small\u2010RNA sequencing on serum from 33 DLBCL patients. Among the identified miRNAs, the combined expression of three of them improved the predictive performance and was correlated with PFS. Two out of three miRNAs, miR\u2010421 and miR\u2010324\u20105p, were also differentially expressed in tumour tissues based on treatment response. Overexpressing these miRNAs reduced cell proliferation, viability and resistance to R\u2010CHOP in the germinal centre B\u2010like COO subtype. <jats:italic>EGLN1<\/jats:italic> and <jats:italic>TXNRD1<\/jats:italic>, regulators of oxygen metabolism and redox homeostasis, were identified as miRNA targets and the silencing or inhibition of these genes impaired cell viability and induced ferroptosis. These results support the application of a two\u2010miRNA signature and its targets for novel combined therapeutic interventions in DLBCL.<\/jats:p>","DOI":"10.1111\/bjh.70017","type":"journal-article","created":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T06:34:55Z","timestamp":1753079695000},"page":"802-812","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A predictive serum <scp>miRNA<\/scp> signature impacts diffuse large B\u2010cell lymphoma cell viability via inhibition of <scp>EGLN1<\/scp> and <scp>TXNRD1<\/scp> regulators of ferroptosis"],"prefix":"10.1111","volume":"207","author":[{"given":"Giulia","family":"Regazzo","sequence":"first","affiliation":[{"name":"Department of Research, Advanced Diagnostics and Technological Innovation, Translational Oncology Research Unit IRCCS \u2010 Regina Elena National Cancer Institute  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Vari","sequence":"additional","affiliation":[{"name":"Department of Research, Advanced Diagnostics and Technological Innovation, Translational Oncology Research Unit IRCCS \u2010 Regina Elena National Cancer Institute  Rome Italy"},{"name":"Department of Molecular Medicine Sapienza University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6353-2272","authenticated-orcid":false,"given":"Francesco","family":"Marchesi","sequence":"additional","affiliation":[{"name":"Hematology Unit IRCCS \u2010 Regina Elena National Cancer Institute  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Bel\u00e9n","family":"D\u00edaz M\u00e9ndez","sequence":"additional","affiliation":[{"name":"Department of Research, Advanced Diagnostics and Technological Innovation, Translational Oncology Research Unit IRCCS \u2010 Regina Elena National Cancer Institute  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Di Giuliani","sequence":"additional","affiliation":[{"name":"Department of Research, Advanced Diagnostics and Technological Innovation, Translational Oncology Research Unit IRCCS \u2010 Regina Elena National Cancer Institute  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Sacconi","sequence":"additional","affiliation":[{"name":"Biostatistics and Bioinformatics Unit, Clinical Trial Center IRCCS \u2010 Regina Elena National Cancer Institute  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Palombi","sequence":"additional","affiliation":[{"name":"Hematology Unit IRCCS \u2010 Regina Elena National Cancer Institute  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Lulli","sequence":"additional","affiliation":[{"name":"Department of Oncology and Molecular Medicine Istituto Superiore di Sanit\u00e0  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frauke","family":"Goeman","sequence":"additional","affiliation":[{"name":"SAFU Unit IRCCS \u2010 Regina Elena National Cancer Institute  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariangela","family":"Novello","sequence":"additional","affiliation":[{"name":"Pathology Unit IRCCS \u2010 Regina Elena National Cancer Institute  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Tomassi","sequence":"additional","affiliation":[{"name":"Hematology Unit IRCCS \u2010 Regina Elena National Cancer Institute  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Papa","sequence":"additional","affiliation":[{"name":"Hematology Unit IRCCS \u2010 Regina Elena National Cancer Institute  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Bertoni","sequence":"additional","affiliation":[{"name":"Institute of Oncology Research, Faculty of Biomedical Sciences USI Bellinzona  Bellinzona Switzerland"},{"name":"Oncology Institute of Southern Switzerland, Ente Ospedaliero Cantonale Bellinzona  Bellinzona Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Hohaus","sequence":"additional","affiliation":[{"name":"Department of Radiological and Hematological Sciences Universit\u00e0 Cattolica del Sacro Cuore  Rome Italy"},{"name":"Extramedullary Lymphoproliferative Disorders Unit Fondazione Policlinico Universitario Agostino Gemelli IRCCS  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Mengarelli","sequence":"additional","affiliation":[{"name":"Hematology Unit IRCCS \u2010 Regina Elena National Cancer Institute  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5009-2412","authenticated-orcid":false,"given":"Maria Giulia","family":"Rizzo","sequence":"additional","affiliation":[{"name":"Department of Research, Advanced Diagnostics and Technological Innovation, Translational Oncology Research Unit IRCCS \u2010 Regina Elena National Cancer Institute  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,7,20]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00277-024-05880-z"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1080\/17474086.2022.2124156"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2024.04.005"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11912-021-01155-2"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2021.107924"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/diagnostics11101739"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.17734"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2020.100776"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-018-0768-5"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-023-02639-8"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22031176"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pharmtox-052220-102509"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.19988"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2014.00149"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-020-01550-w"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/2162-3619-1-2"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.98846"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-024-06939-5"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph15060734"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41374-020-00495-0"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2021.101949"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2019.101328"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000029242"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.28353"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.7150\/jca.99561"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11011-022-01040-2"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-021-03139-z"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.3390\/biology13070487"},{"issue":"4","key":"e_1_2_12_30_1","first-page":"5331","article-title":"MicroRNA\u2010324\u20105p suppresses the migration and invasion of MM cells by inhibiting the SCF\u03b2\u2010TrCP E3 ligase","volume":"16","author":"Zhang L","year":"2018","journal-title":"Oncol Lett"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0005532"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0013247"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1596"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.acr.2017.07.005"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom12111581"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-022-02378-8"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2019.02.019"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms252111384"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/mco2.70010"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020009404"}],"container-title":["British Journal of Haematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bjh.70017","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T02:45:58Z","timestamp":1757990758000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bjh.70017"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,20]]},"references-count":39,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,9]]}},"alternative-id":["10.1111\/bjh.70017"],"URL":"https:\/\/doi.org\/10.1111\/bjh.70017","archive":["Portico"],"relation":{},"ISSN":["0007-1048","1365-2141"],"issn-type":[{"value":"0007-1048","type":"print"},{"value":"1365-2141","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,20]]},"assertion":[{"value":"2025-02-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-08","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}