Genetic and Epigenetic Silencing of MicroRNA-203 Enhances ABL1 and BCR-ABL1 Oncogene Expression
Copyright policy )Genetic and Epigenetic Silencing of MicroRNA-203 Enhances ABL1 and BCR-ABL1 Oncogene Expression
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.
- Autonomous University of Madrid Spain
- The Ohio State University United States
- The Ohio State University at Marion United States
- University of Ferrara Italy
- Spanish National Research Council Spain
Cancer Research, Fusion Proteins, bcr-abl, Loss of Heterozygosity, CELLCYCLE, Lymphoma, T-Cell, CELLCYCLE;, Cell Line, Tumor, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Animals, Humans, Gene Silencing, Enzyme Inhibitors, 3' Untranslated Regions, DNA Modification Methylases, Cell Proliferation, Chromosomes, Human, Pair 14, Gene Expression Regulation, Leukemic, Gene Expression Profiling, Cell Biology, DNA Methylation, Chromosomes, Mammalian, Lymphoproliferative Disorders, Gene Expression Regulation, Neoplastic, Oncology, Azacitidine
Cancer Research, Fusion Proteins, bcr-abl, Loss of Heterozygosity, CELLCYCLE, Lymphoma, T-Cell, CELLCYCLE;, Cell Line, Tumor, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Animals, Humans, Gene Silencing, Enzyme Inhibitors, 3' Untranslated Regions, DNA Modification Methylases, Cell Proliferation, Chromosomes, Human, Pair 14, Gene Expression Regulation, Leukemic, Gene Expression Profiling, Cell Biology, DNA Methylation, Chromosomes, Mammalian, Lymphoproliferative Disorders, Gene Expression Regulation, Neoplastic, Oncology, Azacitidine
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