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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Vydáno v:	Nature communications Ročník 7; číslo 1; s. 11452
Hlavní autoři:	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
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	London Nature Publishing Group UK 26.04.2016 Nature Publishing Group Nature Portfolio
Témata:	13 14 38 631/337/384/331 631/67/1059 631/67/1990/283/1897 631/80/86 64 96 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
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Shrnutí:	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.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	2041-1723 2041-1723
DOI:	10.1038/ncomms11452