Dataset Information

Decitabine Induces Cell Differentiation and Growth Inhibition that Accompanies Up-regulation of microRNA-143 and MS4A3 in MDS-derived leukemic cell line, MDS-L.

ABSTRACT: Myelodysplastic syndromes (MDS) are a group of clonal myeloid neoplasms characterized by ineffective hematopoiesis and cytopenia. Hypomethylating agents (HMAs) play a central role in the treatment of high-risk MDS, but their mechanisms of action are diverse and not fully understood. To investigate the molecular mechanisms of HMA, an MDS cell line (MDS-L) was cultured with a non-toxic concentration of decitabine for 6 months and drug sensitivity, cell differentiation, and DNA methylation profiles were evaluated. Cells with long-term exposure to decitabine (MDS-L-DAC) were morphologically mature with nuclear lobulation and cytoplasmic granulation, accompanied by decreased expression of the CD34 surface antigen. MDS-L-DAC cells exhibited decreased WT1 expression and intense induction of apoptosis by DAC. DNA methylation array analysis revealed the demethylation of the membrane spanning 4-domains A3 (MS4A3) genes and microRNA-143 (MIR143) in MDS-L-DAC cells. MIR143 functions as a tumor suppressor through the MAPK/ERK pathway, and in MDS-L-DAC cells, decreased expression of KRAS and β-catenin was observed in response to the increased expression of MIR143. The differentiation of MDS cells and decreased expression of WT1 induced by long-term incubation with DAC may involve the restoration of function via demethylation of the MIR143 and MS4A3 gene promoters, which may contribute to eliminating the malignant phenotype through reductions in KRAS and β-catenin expression.

ORGANISM(S): Homo sapiens

PROVIDER: GSE293053 | GEO | 2025/04/06

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Purpose: We aimed to investigate the effect of several anti-leukemia drugs in combination with decitabine (DAC) on the proliferation of myeloid leukemia cells in vitro and in vivo, to select the most efficient combination group and explore associated mechanisms of these combination therapies. Experimental Design: After comparing with five anti-leukemia drugs in several different kinds of cell lines, the combination effect of idarubicin (IDA) with DAC was best. In vivo, by using microPET, TUNEL, and transmission electron microscopy, the inhibitory effects obtained by sequentially combining DAC with IDA, evidenced by evaluating tumor cell proliferation and cell apoptosis. Molecular studies were conducted using gene chip, which was used to explore associated pathways, and real-time quantitative reverse transcription-PCR, western blot and immunohistochemistry (IHC), used to assess regulation of Wnt/β-catenin pathway. Results: The sequential combination of DAC and IDA showed synergistic induction of cell death in U937, HEL, SKM-1 and cells isolated from AML patients. Importantly, the inhibition of tumor growth in the sequential combination group was found to be significantly higher than that of single drug group or control group in vivo. Moreover, sequential treatment with DAC and IDA induced apoptosis and depression of the Wnt/β-catenin pathway in both culture and animal studies. Conclusions: Our findings showed that sequentially combining decitabine with idarubicin had a synergistic anti-leukemia effect. These findings were attributed to demethylation of Wnt pathway inhibitors and downregulation of Wnt pathway nuclear targets observed in vitro and in vivo. After comparing with five anti-leukemia drugs in several different kinds of cell lines, the combination effect of idarubicin (IDA) with DAC was best. In vivo, by using microPET, TUNEL, and transmission electron microscopy, the inhibitory effects obtained by sequentially combining DAC with IDA, evidenced by evaluating tumor cell proliferation and cell apoptosis. Molecular studies were conducted using gene chip, which was used to explore associated pathways, and real-time quantitative reverse transcription-PCR, western blot and immunohistochemistry (IHC), used to assess regulation of Wnt/β-catenin pathway.

Dataset Information

Decitabine Induces Cell Differentiation and Growth Inhibition that Accompanies Up-regulation of microRNA-143 and MS4A3 in MDS-derived leukemic cell line, MDS-L.

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets