{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T00:30:42Z","timestamp":1768005042951,"version":"3.49.0"},"reference-count":33,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2021,2,10]],"date-time":"2021-02-10T00:00:00Z","timestamp":1612915200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81870138"],"award-info":[{"award-number":["81870138"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>T cell acute lymphoblastic leukaemia (T\u2010ALL) is a highly aggressive haematological cancer of the bone marrow. The abnormal expression of microRNAs (miRNAs) is reportedly involved in T\u2010ALL development and progression. Thus, we aimed to decipher the involvement of miR\u2010204 silencing mediated by DNA methylation in the occurrence of T cell acute lymphoblastic leukaemia (T\u2010ALL). miR\u2010204 expression was determined in bone marrow and peripheral blood samples from T\u2010ALL patients by real\u2010time quantitative PCR (RT\u2010qPCR) with its effect on cell proliferation evaluated by functional assays. In addition, bisulphite sequencing PCR was employed to detect the DNA methylation level of the miR\u2010204 promoter region, and the binding site between miR\u2010204 and IRAK1 was detected by luciferase assay. We found that miR\u2010204 was down\u2010regulated in T cells of T\u2010ALL patients, which was caused by the increased DNA methylation in the promoter region of miR\u2010204. Moreover, overexpression of miR\u2010204 inhibited T\u2010ALL cell proliferation while enhancing their apoptosis through interleukin receptor\u2010associated kinase 1 (IRAK1), which enhanced the expression of matrix metalloproteinase\u20102 (MMP\u20102) and MMP\u20109 through activation of p\u2010p65. Thus, miR\u2010204 modulated MMP\u20102 and MMP\u20109 through IRAK1\/NF\u2010\u03baB signalling pathway, which was confirmed by in vivo assay. Taken together, DNA methylation\u2010mediated miR\u2010204 silencing increased the transcription of IRAK1, thus activating the NF\u2010\u03baB signalling pathway and up\u2010regulating the downstream targets MMP\u20102\/MMP\u20109.<\/jats:p>","DOI":"10.1111\/jcmm.15896","type":"journal-article","created":{"date-parts":[[2021,2,11]],"date-time":"2021-02-11T04:42:12Z","timestamp":1613018532000},"page":"2365-2376","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["DNA methylation\u2010mediated silencing of microRNA\u2010204 enhances T cell acute lymphoblastic leukemia by up\u2010regulating MMP\u20102 and MMP\u20109 via NF\u2010\u03baB"],"prefix":"10.1111","volume":"25","author":[{"given":"Congmeng","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Hematology Zhangzhou Affiliated Hospital of Fujian Medical University  Zhangzhou 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