miR-22 has a potent anti-tumour role with therapeutic potential in acute myeloid leukaemia

MicroRNAs are subject to precise regulation and have key roles in tumorigenesis. In contrast to the oncogenic role of miR-22 reported in myelodysplastic syndrome (MDS) and breast cancer, here we show that miR-22 is an essential anti-tumour gatekeeper in de novo acute myeloid leukaemia (AML) where it...

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Veröffentlicht in:Nature communications Jg. 7; H. 1; S. 11452
Hauptverfasser: Jiang, Xi, Hu, Chao, Arnovitz, Stephen, Bugno, Jason, Yu, Miao, Zuo, Zhixiang, Chen, Ping, Huang, Hao, Ulrich, Bryan, Gurbuxani, Sandeep, Weng, Hengyou, Strong, Jennifer, Wang, Yungui, Li, Yuanyuan, Salat, Justin, Li, Shenglai, Elkahloun, Abdel G., Yang, Yang, Neilly, Mary Beth, Larson, Richard A., Le Beau, Michelle M., Herold, Tobias, Bohlander, Stefan K., Liu, Paul P., Zhang, Jiwang, Li, Zejuan, He, Chuan, Jin, Jie, Hong, Seungpyo, Chen, Jianjun
Format: Journal Article
Sprache:Englisch
Veröffentlicht: London Nature Publishing Group UK 26.04.2016
Nature Publishing Group
Nature Portfolio
Schlagworte:
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631/337/384/331
631/67/1059
631/67/1990/283/1897
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Acute Disease
Animals
Breast cancer
Cell Line
Cell Line, Tumor
Cell Proliferation - genetics
Down-Regulation
Epigenesis, Genetic
Epigenetics
Gene Expression Profiling
Gene Expression Regulation, Leukemic
Genes, Tumor Suppressor
HEK293 Cells
Hematology
Humanities and Social Sciences
Humans
Leukemia
Leukemia, Myeloid - drug therapy
Leukemia, Myeloid - genetics
Leukemia, Myeloid - pathology
Medicine
Mice, Inbred C57BL
MicroRNAs
MicroRNAs - chemistry
MicroRNAs - genetics
MicroRNAs - therapeutic use
multidisciplinary
Mutation
Myelodysplastic syndromes
Myelodysplastic Syndromes - genetics
Myelodysplastic Syndromes - pathology
Oncology
Pathogenesis
Roles
Science
Science (multidisciplinary)
Signal Transduction - genetics
Chicago Illinois
United States > US
Illinois
China
ISSN:2041-1723, 2041-1723
Online-Zugang:Volltext
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Zusammenfassung:MicroRNAs are subject to precise regulation and have key roles in tumorigenesis. In contrast to the oncogenic role of miR-22 reported in myelodysplastic syndrome (MDS) and breast cancer, here we show that miR-22 is an essential anti-tumour gatekeeper in de novo acute myeloid leukaemia (AML) where it is significantly downregulated. Forced expression of miR-22 significantly suppresses leukaemic cell viability and growth in vitro , and substantially inhibits leukaemia development and maintenance in vivo . Mechanistically, miR-22 targets multiple oncogenes, including CRTC1 , FLT3 and MYCBP , and thus represses the CREB and MYC pathways. The downregulation of miR-22 in AML is caused by TET1/GFI1/EZH2/SIN3A-mediated epigenetic repression and/or DNA copy-number loss. Furthermore, nanoparticles carrying miR-22 oligos significantly inhibit leukaemia progression in vivo . Together, our study uncovers a TET1/GFI1/EZH2/SIN3A/miR-22/CREB-MYC signalling circuit and thereby provides insights into epigenetic/genetic mechanisms underlying the pathogenesis of AML, and also highlights the clinical potential of miR-22-based AML therapy. Mir-22 has been shown to be an oncogenic microRNA in breast cancer and myelodysplastic syndrome. Here, the authors show that mir-22 functions as a tumour suppressor in de novo acute myeloid leukaemia by inhibiting the expression of several oncogenes and that restoring mir-22 expression suppresses AML progression.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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ISSN:2041-1723
2041-1723
DOI:10.1038/ncomms11452