{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T01:55:16Z","timestamp":1773366916479,"version":"3.50.1"},"reference-count":90,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T00:00:00Z","timestamp":1773100800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002426","name":"Telethon Foundation","doi-asserted-by":"publisher","award":["GGP20046"],"award-info":[{"award-number":["GGP20046"]}],"id":[{"id":"10.13039\/501100002426","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>\u03b2-thalassaemia (\u03b2-thal) is part of a group of diseases, the \u03b2-hemoglobinopathies, affecting the levels or functionality of the \u03b2-globin subunit of hemoglobin, which are the most widespread monogenic diseases throughout the world. The severity of \u03b2-thal is determined by different genetic factors, but in the gravest form, affected patients are constrained to a program of blood transfusion and iron chelation regimens for their entire life. Although definitive cures, such as bone marrow transplantation or gene therapy, are now available, they are still far from being applied worldwide. Therefore, there is growing attention towards the use of drugs to cure or ameliorate \u03b2-thal disorder. Among all the strategies, pharmacological increase of fetal HbF and\/or adult HbA2 can represent an advantageous approach as high levels of both hemoglobins are effective against \u03b2-thal. Therefore, the identification of therapeutic targets that can modulate, by the use of drugs, these hemoglobins is increasingly urgent. In this paper, we analyze the effects of the absence of the CCND3 gene, a druggable target associated with HbF and HbA2 levels, in a humanized mouse model of \u03b2-thal to assess the impact against the disorder. Upregulation of \u03b3- and \u03b4-globin levels in mice lacking Ccnd3 expression contributes to partial restoration of the \u03b1\/\u03b2 balance, with a consequent increase in hemoglobin levels, improvement of iron levels, and reduction of splenomegaly. Moreover, we present data supporting the enhancement of erythropoiesis. Our data indicate the CCND3 gene as a possible target for drugs against \u03b2-thal.<\/jats:p>","DOI":"10.3390\/cells15060495","type":"journal-article","created":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T17:04:24Z","timestamp":1773162264000},"page":"495","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["CCND3 Suppression Ameliorates \u03b2-Thalassaemia in a Murine Disease Model: A Potential Therapeutic Strategy"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6806-3492","authenticated-orcid":false,"given":"Cristian Antonio","family":"Caria","sequence":"first","affiliation":[{"name":"Istituto di Ricerca Genetica e Biomedica, Cittadella Universitaria di Monserrato, SS 554, Bivio Sestu Km 4.500, 09042 Cagliari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Franca","family":"Marongiu","sequence":"additional","affiliation":[{"name":"Istituto di Ricerca Genetica e Biomedica, Cittadella Universitaria di Monserrato, SS 554, Bivio Sestu Km 4.500, 09042 Cagliari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susanna","family":"Porcu","sequence":"additional","affiliation":[{"name":"Istituto di Ricerca Genetica e Biomedica, Cittadella Universitaria di Monserrato, SS 554, Bivio Sestu Km 4.500, 09042 Cagliari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela","family":"Poddie","sequence":"additional","affiliation":[{"name":"Istituto di Ricerca Genetica e Biomedica, Cittadella Universitaria di Monserrato, SS 554, Bivio Sestu Km 4.500, 09042 Cagliari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simona","family":"Vaccargiu","sequence":"additional","affiliation":[{"name":"Istituto di Ricerca Genetica e Biomedica, Cittadella Universitaria di Monserrato, SS 554, Bivio Sestu Km 4.500, 09042 Cagliari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jim","family":"Vadolas","sequence":"additional","affiliation":[{"name":"Centre for Cancer Research, Hudson Institute of Medical Research, Melbourne 3168, Australia"},{"name":"Department of Molecular and Translational Science, Monash University, Melbourne 3168, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandra","family":"Meloni","sequence":"additional","affiliation":[{"name":"Istituto di Ricerca Genetica e Biomedica, Cittadella Universitaria di Monserrato, SS 554, Bivio Sestu Km 4.500, 09042 Cagliari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucia","family":"Perseu","sequence":"additional","affiliation":[{"name":"Istituto di Ricerca Genetica e Biomedica, Cittadella Universitaria di Monserrato, SS 554, Bivio Sestu Km 4.500, 09042 Cagliari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4238-3233","authenticated-orcid":false,"given":"Alessandra","family":"Olianas","sequence":"additional","affiliation":[{"name":"Department of Life and Environmental Sciences, Statal University of Cagliari, 09042 Monserrato, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4122-9293","authenticated-orcid":false,"given":"Maria Serafina","family":"Ristaldi","sequence":"additional","affiliation":[{"name":"Istituto di Ricerca Genetica e Biomedica, Cittadella Universitaria di Monserrato, SS 554, Bivio Sestu Km 4.500, 09042 Cagliari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/1750-1172-5-11","article-title":"Beta-Thalassemia","volume":"5","author":"Galanello","year":"2010","journal-title":"Orphanet J. 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