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An oncogenic role of miR-142-3p in human T-cell acute lymphoblastic leukemia (T-ALL) by targeting glucocorticoid receptor-alpha and cAMP/PKA pathways
Lv, M.1,2; Zhang, X.2; Jia, H.3; Li, D.1; Zhang, B.1; Zhang, H.1; Hong, M.4; Jiang, T.3; Jiang, Q.2; Lu, J.2; Huang, X.2; Huang, B.1
关键词Mir-142-3p T-leukemic Cells Oncogene Camp/pka Glucocorticoid Receptor
刊名LEUKEMIA
2012-04-01
DOI10.1038/leu.2011.273
26期:4页:769-777
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Oncology ; Hematology
研究领域[WOS]Oncology ; Hematology
关键词[WOS]NF-KAPPA-B ; PROTEIN-KINASE-A ; INDUCED APOPTOSIS ; DIFFERENTIAL EXPRESSION ; SIGNALING PATHWAY ; MICRORNAS ; RESISTANCE ; MECHANISMS ; ACTIVATION ; MALIGNANCIES
英文摘要

MicroRNAs (miRNAs) are a family of 19-24 nucleotide non-coding RNAs with posttranscriptional regulatory functions. The involvement of miRNAs in normal hematopoiesis implies that deregulated miRNAs might contribute to leukemogenesis. To date, although certain miRNAs have been established a clear oncogenic role in hematological malignancies, other individual miRNAs potentially involved in human leukemogenesis still remain elusive. In this report, we showed that miR-142-3p was upregulated in human T-leukemic cell lines and primary T-leukemic cells isolated from T-cell acute lymphoblastic leukemia (T-ALL) patients and its expressive levels were correlated with patients′ prognosis. Such an oncogenic role of miR-142-3p could be explained by its targeting cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) and glucocorticoid receptor alpha (GR alpha). High levels of miR-142-3p resulted in low levels of cAMP and weak activity of PKA, thus relieving the inhibitory effect of PKA on T-leukemic cell proliferation. Meanwhile, miR-142-3p decreased GR alpha protein expression by directly targeting the 3′-untranslational region of GR alpha mRNA, leading to glucocorticoid resistance. Transfection of the miR-142-3p inhibitor effectively converted glucocorticoid resistance, because of the resultant increase of GR alpha expression and PKA activity. These findings suggest that miR-142-3p is critical in T-cell leukemogenesis and may serve as a potential therapeutic target in T-ALL patients. Leukemia (2012) 26, 769-777; doi:10.1038/leu.2011.273; published online 7 October 2011

语种英语
WOS记录号WOS:000302788300024
项目编号30911120482 ; 30770911 ; 81070449 ; NCET-08-0219 ; 7112139
资助机构National Natural Science Foundation of China ; National Science Foundation of China ; Program for New Century Excellent Talents in University ; Beijing Natural Science Foundation
引用统计
被引频次:92[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/57363
专题北京大学第二临床医学院_血液科
北京大学基础医学院
作者单位1.Huazhong Univ Sci & Technol, Tongji Med Coll, Dept Biochem & Mol Biol, Wuhan 430030, Peoples R China
2.Peking Univ, Peoples Hosp, Inst Hematol, Beijing 100871, Peoples R China
3.Huazhong Univ Sci & Technol, Coll Life Sci & Technol, Dept Biol Sci, Wuhan 430030, Peoples R China
4.Huazhong Univ Sci & Technol, Tongji Med Coll, Union Hosp, Dept Hematol, Wuhan 430030, Peoples R China
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Lv, M.,Zhang, X.,Jia, H.,et al. An oncogenic role of miR-142-3p in human T-cell acute lymphoblastic leukemia (T-ALL) by targeting glucocorticoid receptor-alpha and cAMP/PKA pathways[J]. LEUKEMIA,2012,26(4):769-777.
APA Lv, M..,Zhang, X..,Jia, H..,Li, D..,Zhang, B..,...&Huang, B..(2012).An oncogenic role of miR-142-3p in human T-cell acute lymphoblastic leukemia (T-ALL) by targeting glucocorticoid receptor-alpha and cAMP/PKA pathways.LEUKEMIA,26(4),769-777.
MLA Lv, M.,et al."An oncogenic role of miR-142-3p in human T-cell acute lymphoblastic leukemia (T-ALL) by targeting glucocorticoid receptor-alpha and cAMP/PKA pathways".LEUKEMIA 26.4(2012):769-777.
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