{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T01:04:45Z","timestamp":1781831085840,"version":"3.54.5"},"reference-count":35,"publisher":"S. Karger AG","issue":"1","license":[{"start":{"date-parts":[[2021,11,29]],"date-time":"2021-11-29T00:00:00Z","timestamp":1638144000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2021,11,29]],"date-time":"2021-11-29T00:00:00Z","timestamp":1638144000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Chemotherapy"],"published-print":{"date-parts":[[2022]]},"abstract":"<b><i>Introduction:<\/i><\/b> The chemoresistance mechanism of diffuse large B-cell lymphoma (DLBCL) is still poorly understood, and patient prognosis remains unsatisfactory. This study aimed to investigate drug resistance mechanisms in non-germinal center B-cell-like (non-GCB) DLBCL. <b><i>Methods:<\/i><\/b> Doxorubicin (DOX)-resistant OCI-Ly3 cells were generated through long-term incubation of cells in a medium with gradually increasing DOX concentrations. The expression levels of genes related to drug metabolism were determined using a functional gene grouping polymerase chain reaction (PCR) array. Drug-resistant proteins were identified using bioinformatics, and molecular association networks were subsequently generated. The association and mechanism of key genes were determined using a dual-luciferase reporter assay System and chromatin immunoprecipitation (ChIP). The expression of drug-resistant genes and target genes was then measured using Western blotting and immunohistochemistry. The correlation between gene expressions was analyzed using Spearman\u2019s rank correlation coefficient. <b><i>Results:<\/i><\/b> Using the PCR array, <i>MDR1<\/i> was identified as the key gene that regulates DOX resistance in OCI-Ly3\/DOX-A100, a non-GCB DLBCL cell line. The dual-luciferase reporter assay system demonstrated that <i>MDR1<\/i> transcription could be inhibited by PRDM1. ChIP results showed that PRDM1 had the ability to bind to the promoter region (\u22121,132 to \u2212996) of <i>MDR1<\/i>. In OCI-Ly3\/DOX cells, NF-\u03baB activity and PRDM1 expression decreased with an increase in drug-resistant index, whereas <i>MDR1<\/i> expression increased with enhanced drug resistance. Immunohistochemical analysis revealed that relative <i>MDR1<\/i> expression was higher than that of PRDM1 in human DLBCL tissue samples. A negative correlation was observed between MDR1 and PRDM1. <b><i>Conclusion:<\/i><\/b> In non-GCB DLBCL cells, NF-\u03baB downregulates PRDM1 and thereby promotes <i>MDR1<\/i> transcription by terminating PRDM1-induced transcriptional inhibition of <i>MDR1<\/i>. Such a mechanism may explain the reason for disease recurrence in non-GCB DLBCL after R-CHOP or combined CHOP with bortezomib treatment. Our findings may provide a potential therapeutic strategy for reducing drug resistance in patients with DLBCL. <\/jats:p>","DOI":"10.1159\/000520070","type":"journal-article","created":{"date-parts":[[2022,2,8]],"date-time":"2022-02-08T09:51:21Z","timestamp":1644313881000},"page":"12-23","source":"Crossref","is-referenced-by-count":6,"title":["Dysregulated MDR1 by PRDM1\/Blimp1 Is Involved in the Doxorubicin Resistance of Non-Germinal Center B-Cell-Like Diffuse Large B-Cell Lymphoma"],"prefix":"10.1159","volume":"67","author":[{"given":"Kai","family":"Qing","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zizhen","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenfang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunxiang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lining","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongming","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rufang","family":"Xiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shishuang","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ran","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ge","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Xue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junmin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"127","published-online":{"date-parts":[[2021,11,29]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21492"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1038\/35000501"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1007\/s12325-017-0612-x"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbcan.2018.01.001"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-03-769620"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-18-0781"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000013046"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-019-0661-z"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-019-0489-6"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2010.01101.x"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00670-09"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1038\/77861"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1007\/s12026-015-8694-5"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-18652-9"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.3109\/10428194.2014.953155"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2016.243"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1111\/ijcp.13594"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.25666"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.173.9.5556"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.3109\/10428194.2010.551793"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1007\/s00277-015-2467-z"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.5732\/cjc.011.10420"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2011.35.4423"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.3109\/10428194.2012.736980"},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.1007\/s13277-015-3636-3"},{"key":"ref26","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2018.08.010"},{"key":"ref27","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-016-0327-x"},{"key":"ref28","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3884"},{"key":"ref29","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.13101"},{"key":"ref30","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.30792"},{"key":"ref31","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-10-676700"},{"key":"ref32","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-09-049189"},{"key":"ref33","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2010.10.030"},{"key":"ref34","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/484537"},{"key":"ref35","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-08-108654"}],"container-title":["Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/520070","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/520070","content-type":"unspecified","content-versi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