期刊
ONCOTARGET
卷 8, 期 44, 页码 76174-76188出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.19192
关键词
CML; STAT5; miR-21; microRNA; leukemia
资金
- SIRIC BRIO (Bordeaux Recherche Integree en Oncologie)
- Institut National de la Sante et de la Recherche Medicale (INSERM)
- University of Bordeaux
- Federative Research Structure
- Ligue Nationale contre le Cancer (comites Landes and Charentes)
MicroRNAs (miRNAs) are regulators of several key patho-physiological processes, including cell cycle and apoptosis. Using microarray-based miRNA profiling in K562 cells, a model of chronic myeloid leukemia (CML), we found that the oncoprotein BCR-ABL1 regulates the expression of miR-21, an onco-microRNA, found to be overexpressed in several cancers. This effect relies on the presence of two STAT binding sites on the promoter of miR-21, and on the phosphorylation status of STAT5, a transcription factor activated by the kinase activity of BCR-ABL1. Mir-21 regulates the expression of PDCD4 (programmed cell death protein 4), a tumor suppressor identified through a proteomics approach. The phosphoSTAT5 - miR-21 - PDCD4 pathway was active in CML primary CD34(+) cells, but also in acute myeloid leukemia (AML) models like MV4.11 and MOLM13, where the constitutively active tyrosine kinase FLT3-ITD plays a similar role to BCR-ABL1 in the K562 cell line.
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