TY - JOUR
T1 - Genetic and Epigenetic Silencing of MicroRNA-203 Enhances ABL1 and BCR-ABL1 Oncogene Expression
AU - Bueno, María J.
AU - Pérez de Castro, Ignacio
AU - Gómez de Cedrón, Marta
AU - Santos, Javier
AU - Calin, George A.
AU - Cigudosa, Juan C C.
AU - Croce, Carlo M.
AU - Fernández-Piqueras, José
AU - Malumbres, Marcos
N1 - Funding Information:
We thank Susana Temiño for excellent technical assistance, M. Guerrero for CGH analysis, and Amaia Lujambio for help with expression assays. We also thank I. Sánchez-García, J. Benitez, R. Villuendas, M.A. Piris, V. Sexl, S. González, and M. Serrano for providing reagents and samples. M.J.B. was supported by a fellowship from the Spanish Ministry of Education and Science. I.P.d.C. is supported by a Ramón y Cajal contract. This work was funded by grants from the Association International for Cancer Research (AICR #08-0188) to M.M.; the European Commission (EURATOM 2003, F16R-CT-2003-508842 to J.S.); the Human Factor, Mobility, and Marie Curie activities of the European Commission (017448-IRG7 to I.P.d.C.); the Foundation Ramón Areces (to I.P.d.C.); the Foundation of the Asociación Española contra el Cáncer (AECC; to M.M.); Foundation Mutua Madrileña Automovilista (to M.M.); and the Ministry of Education and Science (MEC; SAF2006-09437 to J.F.-P., SAF2004-07459 and SAF2007-64571 to I.P.d.C., SAF2005-04340 to J.C.C., and SAF2006-05186 to M.M.). The Cell Division and Cancer Group of the CNIO is supported by the OncoCycle Programme (S-BIO-0283-2006) from the Comunidad de Madrid, and the OncoBIO Consolider-Ingenio 2010 Programme (CSD2007-00017) from the MEC, Madrid.
PY - 2008/6/10
Y1 - 2008/6/10
N2 - The mammalian genome contains several hundred microRNAs that regulate gene expression through modulation of target mRNAs. Here, we report a fragile chromosomal region lost in specific hematopoietic malignancies. This 7 Mb region encodes about 12% of all genomic microRNAs, including miR-203. This microRNA is additionally hypermethylated in several hematopoietic tumors, including chronic myelogenous leukemias and some acute lymphoblastic leukemias. A putative miR-203 target, ABL1, is specifically activated in these hematopoietic malignancies in some cases as a BCR-ABL1 fusion protein (Philadelphia chromosome). Re-expression of miR-203 reduces ABL1 and BCR-ABL1 fusion protein levels and inhibits tumor cell proliferation in an ABL1-dependent manner. Thus, miR-203 functions as a tumor suppressor, and re-expression of this microRNA might have therapeutic benefits in specific hematopoietic malignancies.
AB - The mammalian genome contains several hundred microRNAs that regulate gene expression through modulation of target mRNAs. Here, we report a fragile chromosomal region lost in specific hematopoietic malignancies. This 7 Mb region encodes about 12% of all genomic microRNAs, including miR-203. This microRNA is additionally hypermethylated in several hematopoietic tumors, including chronic myelogenous leukemias and some acute lymphoblastic leukemias. A putative miR-203 target, ABL1, is specifically activated in these hematopoietic malignancies in some cases as a BCR-ABL1 fusion protein (Philadelphia chromosome). Re-expression of miR-203 reduces ABL1 and BCR-ABL1 fusion protein levels and inhibits tumor cell proliferation in an ABL1-dependent manner. Thus, miR-203 functions as a tumor suppressor, and re-expression of this microRNA might have therapeutic benefits in specific hematopoietic malignancies.
KW - CELLCYCLE
UR - http://www.scopus.com/inward/record.url?scp=44449149903&partnerID=8YFLogxK
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U2 - 10.1016/j.ccr.2008.04.018
DO - 10.1016/j.ccr.2008.04.018
M3 - Article
C2 - 18538733
AN - SCOPUS:44449149903
SN - 1535-6108
VL - 13
SP - 496
EP - 506
JO - Cancer cell
JF - Cancer cell
IS - 6
ER -