SLC22A3 methylation-mediated gene silencing predicts adverse prognosis in acute myeloid leukemia
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Published:2022-12
Issue:1
Volume:14
Page:
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ISSN:1868-7075
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Container-title:Clinical Epigenetics
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language:en
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Short-container-title:Clin Epigenet
Author:
Gu Yu,Xu Zi-jun,Zhou Jing-dong,Wen Xiang-mei,Jin Ye,Yuan Qian,Xia Pei-hui,Feng Yuan,Yang Lei,Lin Jiang,Qian Jun
Abstract
Abstract
Background
We screened out several hypermethylated solute carrier (SLC) family genes in acute myeloid leukemia by reduced representation bisulfite sequencing. SLC22A3 encodes an organic cation transport protein, which is critical for drug transportation and cellular detoxification. SLC22A3 is significantly downregulated and associated with tumor progression and worse prognosis in a variety of solid tumors. However, there are no data available regarding the role of SLC22 in AML. This study aimed to explore the regulatory mechanism of DNA methylation on SLC22A3 expression, as well as its clinical significance in AML prognosis.
Results
SLC22A3 was identified as the sole prognosis-associated gene among SLCs based on TCGA and Beat AML databases. Bone marrow mononuclear cells (BMMNCs) from AML, MDS patients, and healthy donors were enrolled in this study. SLC22A3 methylation was significantly increased in AML compared with controls and MDS patients; meanwhile, the expression level of SLC22A3 was decreased. SLC22A3 hypermethylation presented an obvious association with some specific clinical characteristics and affected the survival time of AML patients as an independent risk indicator. SLC22A3 expression changed regularly as the disease complete remissions and relapses. Demethylation drug 5-aza-2′-deoxycytidine (DAC) activated transcription and increased mRNA expression of SLC22A3 in leukemia cell lines and AML fresh BMMNCs. Knockdown of SLC22A3 in leukemia cells enhanced cell proliferation and suppressed cell apoptosis. Data from public programs were used for auxiliary screening of probable molecular mechanisms of SLC22A3 in the antileukemia effect.
Conclusions
Our results showed that increased methylation and decreased expression of SLC22A3 may be indicators of poor prognosis in AML. Methylation-silenced SLC22A3 expression may have potential guiding significance on antileukemia effect of DAC.
Funder
National Natural Science Foundation of China
Research Innovation Program for College Graduates of Jiangsu Province
Zhenjiang Clinical Research Center of Hematology
Social Development Foundation of Zhenjiang
Scientific Research Project of The Fifth 169 Project of Zhenjiang
Medical Innovation Team of Jiangsu Province
Publisher
Springer Science and Business Media LLC
Subject
Genetics (clinical),Developmental Biology,Genetics,Molecular Biology
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