The tumor suppressive role of miRNA-370 by targeting FoxM1 in acute myeloid leukemia

作者: Xiaolu Zhang , Jiping Zeng , Minran Zhou , Bingnan Li , Yuanyuan Zhang

DOI: 10.1186/1476-4598-11-56

关键词: K562 cellsRNA interferenceCell agingEctopic expressionCancer researchBiologyBone marrowmicroRNAAzacitidineImmunologyMyeloid leukemia

摘要: Background: Recent evidence has accumulated that MicroRNA (miRNA) dysregulation occurs in the majority of human malignancies including acute myeloid leukemia (AML) and may contribute to onco-/leukemo-genesis. Methods: The expression levels miR-370 FoxM1 were assessed 48 newly diagnosed AML patients, 40 patients 1 st complete remission (CR) 21 healthy controls. Quantitative real-time PCR, western blots, colony formation assay, β-Galactosidase ( SA-β-Gal) staining used characterize changes induced by overexpression or inhibition FoxM1. Results: We found down-regulation was a frequent event both cell lines primary leukemic cells from with de novo AML. Lower 37 samples compared those bone marrow derived adult individuals. Ectopic HL60 K562 led growth arrest senescence. In contrast, depletion using RNA interference enhanced proliferation cells. Mechanistically, targets transcription factor FoxM1, well established oncogenic promoting cycle progression. Moreover, when treated 5-aza-2 0 -deoxycytidine, DNA methylation inhibitor, up-regulated, which indicates epigenetic silencing Conclusions: Taken together, function as tumor suppressor targeting silence thus leads derepression consequently contributes development

参考文章(41)
R. Garzon, M. Garofalo, M. P. Martelli, R. Briesewitz, L. Wang, C. Fernandez-Cymering, S. Volinia, C.-G. Liu, S. Schnittger, T. Haferlach, A. Liso, D. Diverio, M. Mancini, G. Meloni, R. Foa, M. F. Martelli, C. Mecucci, C. M. Croce, B. Falini, Distinctive microRNA signature of acute myeloid leukemia bearing cytoplasmic mutated nucleophosmin Proceedings of the National Academy of Sciences of the United States of America. ,vol. 105, pp. 3945- 3950 ,(2008) , 10.1073/PNAS.0800135105
Mojca Jongen-Lavrencic, Su Ming Sun, Menno K. Dijkstra, Peter J. M. Valk, Bob Löwenberg, MicroRNA expression profiling in relation to the genetic heterogeneity of acute myeloid leukemia. Blood. ,vol. 111, pp. 5078- 5085 ,(2008) , 10.1182/BLOOD-2008-01-133355
Yael Altuvia, Pablo Landgraf, Gila Lithwick, Naama Elefant, Sebastien Pfeffer, Alexei Aravin, Michael J Brownstein, Thomas Tuschl, Hanah Margalit, Clustering and conservation patterns of human microRNAs Nucleic Acids Research. ,vol. 33, pp. 2697- 2706 ,(2005) , 10.1093/NAR/GKI567
Eva Bandrés, Elena Cubedo, X Agirre, R Malumbres, R Zarate, N Ramirez, A Abajo, A Navarro, Isabel Moreno, M Monzo, Jesús García-Foncillas, Identification by Real-time PCR of 13 mature microRNAs differentially expressed in colorectal cancer and non-tumoral tissues Molecular Cancer. ,vol. 5, pp. 29- 29 ,(2006) , 10.1186/1476-4598-5-29
G. A. Calin, C. D. Dumitru, M. Shimizu, R. Bichi, S. Zupo, E. Noch, H. Aldler, S. Rattan, M. Keating, K. Rai, L. Rassenti, T. Kipps, M. Negrini, F. Bullrich, C. M. Croce, Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia Proceedings of the National Academy of Sciences of the United States of America. ,vol. 99, pp. 15524- 15529 ,(2002) , 10.1073/PNAS.242606799
Matthew N. Poy, Lena Eliasson, Jan Krutzfeldt, Satoru Kuwajima, Xiaosong Ma, Patrick E. MacDonald, Sébastien Pfeffer, Thomas Tuschl, Nikolaus Rajewsky, Patrik Rorsman, Markus Stoffel, A pancreatic islet-specific microRNA regulates insulin secretion Nature. ,vol. 432, pp. 226- 230 ,(2004) , 10.1038/NATURE03076
Jonathan A. Ewald, Joshua A. Desotelle, George Wilding, David F. Jarrard, Therapy-Induced Senescence in Cancer Journal of the National Cancer Institute. ,vol. 102, pp. 1536- 1546 ,(2010) , 10.1093/JNCI/DJQ364
G. A. Calin, C. Sevignani, C. D. Dumitru, T. Hyslop, E. Noch, S. Yendamuri, M. Shimizu, S. Rattan, F. Bullrich, M. Negrini, C. M. Croce, Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers Proceedings of the National Academy of Sciences of the United States of America. ,vol. 101, pp. 2999- 3004 ,(2004) , 10.1073/PNAS.0307323101
Elihu Estey, Hartmut Döhner, Acute myeloid leukaemia The Lancet. ,vol. 368, pp. 1894- 1907 ,(2006) , 10.1016/S0140-6736(06)69780-8