{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T12:37:00Z","timestamp":1777725420024,"version":"3.51.4"},"reference-count":27,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2018,4,1]],"date-time":"2018-04-01T00:00:00Z","timestamp":1522540800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Investigative Medicine"],"published-print":{"date-parts":[[2018,4]]},"abstract":"<jats:p>T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological cancer. Although microRNA (miR)-452 serves as a tumor suppressor in multiple solid tumors, its expression and function in hematological cancers including T-ALL is largely unknown. We measured the expression of miR-452 in 38 T-ALL and 22 normal lymph node samples by real-time PCR analysis. The methylation levels in the promoter of miR-452 were determined using MethyLight assay. The effects of miR-452 overexpression on proliferation, cell cycle distribution, and tumorigenesis were explored. It was found that miR-452 expression levels were significantly lower in T-ALL specimens than in normal lymph node biopsies (P=0.0079). T-ALL specimens had a significantly higher methylation level in the promoter of miR-452 than normal lymph node tissues (P=0.0014). Consistently, miR-452 was downregulated in Jurkat and Molt-4 T-ALL cells, whose expression was restored after treatment with a demethylation agent 5-aza-2\u2032-deoxycytidine. Ectopic expression of miR-452 inhibited the proliferation of Jurkat and Molt-4 cells and induced a G0\/G1 cell cycle arrest. Overexpression of miR-452 suppressed the protein expression of BMI1 in T-ALL cells. Rescue experiments revealed that overexpression of BMI1 partially reversed the growth-suppressive effect of miR-452 on T-ALL cells. Xenograft tumor studies confirmed that overexpression of miR-452 suppressed tumor growth in nude mice and reduced the expression of BMI1. Collectively, miR-452 is epigenetically silenced and targets BMI1 to exert a growth suppressive activity in T-ALL. Restoration of miR-452 expression may represent a promising therapeutic strategy for this malignancy.<\/jats:p>","DOI":"10.1136\/jim-2017-000591","type":"journal-article","created":{"date-parts":[[2018,1,11]],"date-time":"2018-01-11T20:10:21Z","timestamp":1515701421000},"page":"773-779","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":6,"title":["Microrna-452 Exerts Growth-Suppressive Activity against T-Cell Acute Lymphoblastic Leukemia"],"prefix":"10.1177","volume":"66","author":[{"given":"Haihao","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiannan","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, Tongji Hospital, Tongji Medical College, Huazhong 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