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亚油酸酰胺肟和 5-Aza-2'-脱氧胞苷对不同 IL-6 表达骨髓瘤细胞系中 DNMT3B 表达的表观遗传学影响。

The epigenetic impact of suberohydroxamic acid and 5‑Aza‑2'‑deoxycytidine on DNMT3B expression in myeloma cell lines differing in IL‑6 expression.

机构信息

Department of Clinical and Molecular Pathology, Faculty of Medicine and Dentistry, Palacky University Olomouc, 777 15 Olomouc, Czech Republic.

Department of Histology and Embryology, Faculty of Medicine and Dentistry, Palacky University Olomouc, 777 15 Olomouc, Czech Republic.

出版信息

Mol Med Rep. 2022 Oct;26(4). doi: 10.3892/mmr.2022.12837. Epub 2022 Aug 31.

DOI:10.3892/mmr.2022.12837
PMID:36043519
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9471560/
Abstract

Gene inactivation of the cyclin‑dependent kinase inhibitors p16, p15 and p21 is frequently mediated by promoter gene methylation, whereas histone deacetylases (HDACs) control gene expression through their ability to deacetylate proteins. The effect of suberohydroxamic acid (SBHA) and 5‑Aza‑2'‑deoxycytidine (Decitabine) (DAC) treatments on the transcription of , and genes, and their effects on molecular biological behavior were examined in two myeloma cell lines, RPMI8226 and U266, which differ in p53‑functionality and IL‑6 expression. In both tested myeloma cell lines, a non‑methylated state of the gene promoter region was detected with normal gene expression, and the same level of p15 protein was detected by immunocytochemical staining. Furthermore, in myeloma cells treated with SBHA and DAC alone, the expression of both p15 and p21 was significantly upregulated in RPMI8226 cells (p53‑functional, without IL‑6 expression), whereas in the U266 cell line (p53 deleted, expressing IL‑6) only p21 expression was significantly increased. Moreover, the analysis revealed that treatment with DAC induced DNMT3B enhancement in U266 cells. In conclusion, in myeloma cells with IL‑6 expression, significantly increased DNMT3B expression indicated the tumorigenic consequences of 5‑Aza‑2'deoxycytidine treatment, which requires careful use in diseases involving epigenetic dysregulation, such as multiple myeloma (MM).

摘要

细胞周期蛋白依赖性激酶抑制剂 p16、p15 和 p21 的基因失活通常由启动子基因甲基化介导，而组蛋白去乙酰化酶 (HDACs) 通过去乙酰化蛋白质来控制基因表达。本研究在 RPMI8226 和 U266 两种骨髓瘤细胞系中检测了琥珀酰亚胺羟肟酸 (SBHA) 和 5-氮杂-2'-脱氧胞苷 (Decitabine) (DAC) 处理对 、 和 基因转录的影响，以及它们对分子生物学行为的影响。这两种骨髓瘤细胞系中， 基因启动子区域均呈非甲基化状态，基因表达正常，免疫细胞化学染色检测到相同水平的 p15 蛋白。此外，在单独用 SBHA 和 DAC 处理的骨髓瘤细胞中，RPMI8226 细胞（p53 功能正常，无 IL-6 表达）中 p15 和 p21 的表达均显著上调，而 U266 细胞系（p53 缺失，表达 IL-6）中仅 p21 的表达显著上调。此外，分析表明 DAC 处理诱导 U266 细胞中 DNMT3B 增强。总之，在表达 IL-6 的骨髓瘤细胞中，DNMT3B 表达显著增加表明 5-氮杂-2'-脱氧胞苷治疗的致瘤后果，在涉及表观遗传失调的疾病中，如多发性骨髓瘤 (MM)，需要谨慎使用。

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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/330d/9471560/fa3251d80b8c/mmr-26-04-12837-g10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/330d/9471560/33f2426159ec/mmr-26-04-12837-g11.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/330d/9471560/ca4519f5c780/mmr-26-04-12837-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/330d/9471560/4cdc9638120a/mmr-26-04-12837-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/330d/9471560/45fa58e244dc/mmr-26-04-12837-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/330d/9471560/85d3bbcc7970/mmr-26-04-12837-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/330d/9471560/98796768aa61/mmr-26-04-12837-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/330d/9471560/ee7e400ea1fd/mmr-26-04-12837-g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/330d/9471560/cd7d225c97da/mmr-26-04-12837-g06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/330d/9471560/a1e9b3565319/mmr-26-04-12837-g07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/330d/9471560/16bbda9aebc2/mmr-26-04-12837-g08.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/330d/9471560/88d2bd742210/mmr-26-04-12837-g09.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/330d/9471560/fa3251d80b8c/mmr-26-04-12837-g10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/330d/9471560/33f2426159ec/mmr-26-04-12837-g11.jpg

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