Genetic and epigenetic silencing of microRNA-203 enhances ABL1 and BCR-ABL1 oncogene expression
- PMID: 18538733
- DOI: 10.1016/j.ccr.2008.04.018
Genetic and epigenetic silencing of microRNA-203 enhances ABL1 and BCR-ABL1 oncogene expression
Erratum in
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Genetic and Epigenetic Silencing of MicroRNA-203 Enhances ABL1 and BCR-ABL1 Oncogene Expression.Cancer Cell. 2016 Apr 11;29(4):607-608. doi: 10.1016/j.ccell.2016.03.013. Cancer Cell. 2016. PMID: 27070707 No abstract available.
Abstract
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.
Comment in
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Linking miRNA regulation to BCR-ABL expression: the next dimension.Cancer Cell. 2008 Jun;13(6):467-9. doi: 10.1016/j.ccr.2008.05.013. Cancer Cell. 2008. PMID: 18538729
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