{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T03:46:16Z","timestamp":1771559176344,"version":"3.50.1"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2020,6,1]],"date-time":"2020-06-01T00:00:00Z","timestamp":1590969600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2015M581292"],"award-info":[{"award-number":["2015M581292"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31470876"],"award-info":[{"award-number":["31470876"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,6,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Mixed-lineage leukemia 1 (MLL1), which exerts its H3K4 methyltransferase activity by interacting with WDR5, ASH2L, and RBBP5, plays a pivotal role in regulating hematopoietic stem cell homeostasis. Disrupting the integrity of MLL1-complex has been reported to be associated with acute leukemia. However, the exact role of MLL1-complex in myeloid cells is unknown. In this study, microarray analysis revealed that the core components of the Mll1-complex, Wdr5, Ash2l, and Mll1, were concurrently downregulated by tumor-secreted factors as well as GM-CSF + IL-6 during the accumulation and activation of murine myeloid-derived suppressor cells (MDSCs). These changes were further validated by quantitative RT-PCR and Western blotting both in vitro and in vivo. The expression levels of WDR5 and ASH2L were also significantly decreased in bone marrow MDSCs of lung cancer patients compared with that of healthy controls. Functionally, ectopic expression of Wdr5, Ash2l, and Mll1 (C terminus) reversed the accumulation and function of GM-CSF + IL-6\u2013induced as well as tumor-cocultured polymorphonuclear MDSCs (PMN-MDSCs) by promoting them to differentiate into mature neutrophil-like cells. Mechanistically, GM-CSF + IL-6\u2013activated Stat3 and Cebp\u03b2 synergistically induced the expression of miR-21a, miR-21b, and miR-181b, and thus inhibited the expression of Wdr5, Ash2l, and Mll1 by targeting to their 3\u2032 untranslated regions, respectively. Furthermore, knockdown of these microRNAs also suppressed the expansion and function of GM-CSF + IL-6\u2013induced PMN-MDSCs. Taken together, our findings indicate that the Stat3\/Cebp\u03b2\u2013miR-21a\/b\/181b\u2013Mll1-complex axis may play a critical role in PMN-MDSC expansion, activation, and differentiation, and this axis may provide an effectively immunological therapeutic approach for patients with cancer or other immunological diseases.<\/jats:p>","DOI":"10.4049\/jimmunol.2000230","type":"journal-article","created":{"date-parts":[[2020,5,1]],"date-time":"2020-05-01T19:45:14Z","timestamp":1588362314000},"page":"3400-3415","source":"Crossref","is-referenced-by-count":20,"title":["Suppression of Mll1-Complex by Stat3\/Cebp\u03b2\u2013Induced miR-21a\/21b\/181b Maintains the Accumulation, Homeostasis, and Immunosuppressive Function of Polymorphonuclear Myeloid-Derived Suppressor Cells"],"prefix":"10.1093","volume":"204","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1226-4807","authenticated-orcid":false,"given":"Zhiqian","family":"Zhang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Medicinal Chemical Biology, Nankai University , Tianjin 300071 ,","place":["China"]},{"name":"School of Medicine, Southern University of Science and Technology , Shenzhen 518055, Guangdong ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xu","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Harbin Medical University Cancer Hospital , Harbin 150040, Heilongjiang ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enlin","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medicinal Chemical Biology, Nankai University , Tianjin 300071 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yugang","family":"Huang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medicinal Chemical Biology, Nankai University , Tianjin 300071 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rongcun","family":"Yang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medicinal Chemical Biology, Nankai University , Tianjin 300071 ,","place":["China"]},{"name":"Key Laboratory of Bioactive Materials Ministry of Education, Nankai University , Tianjin 300071 ,","place":["China"]},{"name":"Department of Immunology, School of Medicine, Nankai University , Tianjin 300071 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2020,6,15]]},"reference":[{"key":"2025030417512261100_r1","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.3389\/fimmu.2019.01099","article-title":"Myeloid-derived suppressor cells: not only in tumor immunity","volume":"10","author":"Pawelec","year":"2019","journal-title":"Front. 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