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Azacitidine regulates DNA methylation of GADD45γ in myelodysplastic syndromes
- Source :
- Journal of Clinical Laboratory Analysis
- Publication Year :
- 2020
- Publisher :
- Wiley, 2020.
-
Abstract
- Background Myelodysplastic syndrome (MDS) is a heterogeneous clonal disease originated from hematopoietic stem cells. Epigenetic studies had demonstrated that DNA methylation and histone acetylation were abnormal in MDS. Azacitidine is an effective drug in the treatment of demethylation. Methods RT‐PCR was performed to determine GADD45γ in 15 MDS clinical samples. Myelodysplastic syndrome cell lines SKM‐1 and HS‐5 were transfected with GADD45γ eukaryotic expression vector and/or GADD45γ shRNA interference plasmid, and treated with azacitidine. Proliferation and apoptosis were examined by CCK‐8 and Western blot analysis to confirm the function role of GADD45γ and azacitidine. The methylation level of GADD45γ gene was detected by bisulfite conversion and PCR. Results This study found that GADD45γ gene was down‐expressed in MDS patients' bone marrow and MDS cell lines, and the down‐regulation of GADD45γ in MDS could inhibit MDS cell apoptosis and promote proliferation. Azacitidine, a demethylation drug, could restore the expression of GADD45γ in MDS cells and inhibit the proliferation of MDS cells by inducing apoptosis, which was related to prognosis and transformation. Conclusion This study indicated that GADD45γ was expected to become a new target of MDS‐targeted therapy. The findings of this study provided a new direction for the research and development of new MDS clinical drugs, and gave a new idea for the development of MDS demethylation drug to realize precise treatment.<br />Azacitidine Induce MDS cell apoptosis.
- Subjects :
- 0301 basic medicine
Microbiology (medical)
azacitidine
Clinical Biochemistry
Bisulfite sequencing
Azacitidine
Gene Expression
Apoptosis
Bone Marrow Cells
Cell Cycle Proteins
Cell Line
03 medical and health sciences
0302 clinical medicine
hemic and lymphatic diseases
MDS
Humans
Immunology and Allergy
Medicine
Epigenetics
Research Articles
Cell Proliferation
biology
business.industry
Myelodysplastic syndromes
Biochemistry (medical)
Public Health, Environmental and Occupational Health
Genetic Therapy
Hematology
Methylation
DNA Methylation
medicine.disease
Medical Laboratory Technology
030104 developmental biology
Histone
Myelodysplastic Syndromes
030220 oncology & carcinogenesis
DNA methylation
biology.protein
Cancer research
GADD45γ
Stem cell
business
Research Article
medicine.drug
Subjects
Details
- ISSN :
- 10982825 and 08878013
- Volume :
- 35
- Database :
- OpenAIRE
- Journal :
- Journal of Clinical Laboratory Analysis
- Accession number :
- edsair.doi.dedup.....f43d0361e231e1a89681e1410b3989ff