{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T09:11:56Z","timestamp":1790327516401,"version":"4.1.0"},"reference-count":30,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T00:00:00Z","timestamp":1788307200000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2024M761029"],"award-info":[{"award-number":["2024M761029"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical &amp; Translational Med"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Doxorubicin, an anthracycline chemotherapeutic agent, is widely used in diffuse large B\u2011cell lymphoma (DLBCL) treatment, yet its clinical efficacy is often compromised by drug resistance. Protein arginine methyltransferase 7 (PRMT7) is a methyltransferase implicated in tumourigenesis and cancer progression. However, its precise role and underlying mechanisms in DLBCL progression and doxorubicin resistance remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We analysed PRMT7 expression in DLBCL cell lines and patient specimens using bioinformatic databases, western blotting, reverse Transcription Polymerase Chain Reactionand immunohistochemistry. Functional studies were performed in DLBCL cell lines through CRISPR\/Cas9\u2011mediated knockout and overexpression systems, combined with in vitro assays for proliferation, apoptosis and doxorubicin sensitivity, as well as in vivo xenograft models. Mechanistically, co\u2011immunoprecipitation, arginine methylation assays and immunofluorescence were employed to characterise the PRMT7\u2013Forkhead box K (FOXK)1\/2\u2013Dishevelled Segment Polarity Protein 2 (DVL2)\u00a0axis and its modulation of Wnt\/ (beta) \u03b2\u2011catenin signalling. In addition, we designed and evaluated FOXK\u2011methylation\u2011competitive inhibitory peptides for their capacity to sensitise DLBCL cells to doxorubicin.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Our study revealed that PRMT7 is upregulated in DLBCL and promotes both tumour proliferation and doxorubicin resistance. Conversely, knockdown of PRMT7 inhibited DLBCL cell proliferation and enhanced sensitivity to doxorubicin. Mechanistically, PRMT7 catalyses arginine methylation of FOXK1 at arginine (R) 191 and FOXK2 at R144, which markedly increases their binding affinity for DVL2 and facilitates DVL2 nuclear translocation. This event leads to constitutive activation of the Wnt\/\u03b2\u2011catenin signalling pathway. Importantly, we developed a FOXK\u2011derived peptide that competitively inhibits FOXK methylation, suppresses Wnt\/\u03b2\u2011catenin signalling and significantly potentiates the antitumour efficacy of doxorubicin in DLBCL.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings indicate that the PRMT7\/FOXK\/DVL2\/Wnt\u2010\u03b2\u2010catenin axis serves as a novel driver of DLBCL progression and doxorubicin resistance. Targeting the PRMT7\u2013FOXK methylation interface may offer a potential therapeutic approach for overcoming doxorubicin resistance in DLBCL, although further validation in clinical settings is warranted.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Upregulated PRMT7 drives DLBCL progression and doxorubicin resistance<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>PRMT7 methylates FOXK1 at arginine 191 and FOXK2 at arginine 144<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>FOXK1\/2 methylation enhances interaction with DVL2 and promotes nuclear translocation<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>FOXK1\/2 methylation dactivate Wnt\/\u00df-catenin signaling through DVL2 nuclear entry<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>A novel peptide inhibitory blocks FOXK1\/2 methylation and restores doxorubicin sensitivity<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ctm2.70802","type":"journal-article","created":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T09:08:30Z","timestamp":1788340110000},"source":"Crossref","is-referenced-by-count":0,"title":["PRMT7\u2010mediated arginine methylation of FOXK activates Wnt\/\u03b2\u2010catenin signalling to drive doxorubicin resistance in diffuse large B\u2010cell lymphoma"],"prefix":"10.1002","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-6745-0826","authenticated-orcid":false,"given":"Xiaoyan","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9442-2009","authenticated-orcid":false,"given":"Jiasi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Teng","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology  Wuhan 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