Association of expression of epigenetic molecular factors with DNA methylation and sensitivity to chemotherapeutic agents in cancer cell lines.
Association of expression of epigenetic molecular factors with DNA methylation and sensitivity to chemotherapeutic agents in cancer cell lines.
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DOI：
10.1186/s13148-021-01026-4
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发表时间：
2021-03-06
影响因子：
5.7
通讯作者：
Krushkal J
中科院分区：
文献类型：
--
作者：
Vural S;Palmisano A;Reinhold WC;Pommier Y;Teicher BA;Krushkal J
改变的DNA甲基化模式在癌症的发生和发展中起重要作用。我们研究了直接或间接参与DNA甲基化和去甲基化的基因的表达水平是否与癌细胞系对各种抗肿瘤药物化疗的反应有关。我们分析了72个编码表观遗传因子的基因，这些表观遗传因子直接或间接参与DNA甲基化和去甲基化过程。我们研究了它们的预处理表达水平与单个DNA甲基化探针的甲基化β值、基因区域内的平均DNA甲基化和平均表观基因组甲基化水平的相关性。我们分析了来自癌症细胞系百科全书和癌症药物敏感性基因组学数据集的645种癌细胞系和23种癌症类型的数据。我们观察到许多编码表观遗传因子的基因表达与化疗药物反应之间的相关性。编码多种表观遗传因子的基因（包括KDM2B、DNMT 1、EHMT 2、SETDB 1、EZH2、APOBEC3G和其他基因）的表达与对多种药物的反应相关。许多靶探针和基因区域的DNA甲基化与编码表观遗传因子的多个基因的表达相关，强调了多个交叉分子途径对表观基因组甲基化的复杂调控。其表达与多个表观基因组靶标的甲基化相关的基因编码DNA甲基转移酶、泰特DNA甲基胞嘧啶双加氧酶、甲基化DNA结合蛋白ZBTB 38、KDM 2B、SETDB 1以及参与影响DNA甲基化的多种表观遗传过程的其他分子因子。虽然许多表观基因组靶点的基线DNA甲基化与细胞系对抗肿瘤药物的反应相关，但每个表观遗传因子对特定靶点甲基化的重叠效应之间的复杂关系以及这些影响在肿瘤对单个药物反应中的重要性需要进一步研究。编码表观遗传因子的多个基因的表达与药物反应和可能影响对治疗剂的反应的许多表观基因组靶点的DNA甲基化相关。我们的研究结果表明，调节表观基因组中DNA甲基化的复杂和相互关联的途径，可能直接和间接影响对化疗的反应。
Altered DNA methylation patterns play important roles in cancer development and progression. We examined whether expression levels of genes directly or indirectly involved in DNA methylation and demethylation may be associated with response of cancer cell lines to chemotherapy treatment with a variety of antitumor agents. We analyzed 72 genes encoding epigenetic factors directly or indirectly involved in DNA methylation and demethylation processes. We examined association of their pretreatment expression levels with methylation beta-values of individual DNA methylation probes, DNA methylation averaged within gene regions, and average epigenome-wide methylation levels. We analyzed data from 645 cancer cell lines and 23 cancer types from the Cancer Cell Line Encyclopedia and Genomics of Drug Sensitivity in Cancer datasets. We observed numerous correlations between expression of genes encoding epigenetic factors and response to chemotherapeutic agents. Expression of genes encoding a variety of epigenetic factors, including KDM2B, DNMT1, EHMT2, SETDB1, EZH2, APOBEC3G, and other genes, was correlated with response to multiple agents. DNA methylation of numerous target probes and gene regions was associated with expression of multiple genes encoding epigenetic factors, underscoring complex regulation of epigenome methylation by multiple intersecting molecular pathways. The genes whose expression was associated with methylation of multiple epigenome targets encode DNA methyltransferases, TET DNA methylcytosine dioxygenases, the methylated DNA-binding protein ZBTB38, KDM2B, SETDB1, and other molecular factors which are involved in diverse epigenetic processes affecting DNA methylation. While baseline DNA methylation of numerous epigenome targets was correlated with cell line response to antitumor agents, the complex relationships between the overlapping effects of each epigenetic factor on methylation of specific targets and the importance of such influences in tumor response to individual agents require further investigation. Expression of multiple genes encoding epigenetic factors is associated with drug response and with DNA methylation of numerous epigenome targets that may affect response to therapeutic agents. Our findings suggest complex and interconnected pathways regulating DNA methylation in the epigenome, which may both directly and indirectly affect response to chemotherapy.
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影响因子：
11.8
作者：
Cubenas-Potts, Caelin;Matunis, Michael J.
通讯作者：
Matunis, Michael J.
DOI：
10.1038/nrm4043
发表时间：
2015-09
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
Du J;Johnson LM;Jacobsen SE;Patel DJ
通讯作者：
Patel DJ
DOI：
10.1111/cts.12861
发表时间：
2021-01
期刊：
Clinical and translational science
影响因子：
--
作者：
Buelow DR;Anderson JT;Pounds SB;Shi L;Lamba JK;Hu S;Gibson AA;Goodwin EA;Sparreboom A;Baker SD
通讯作者：
Baker SD
影响因子：
3.7
作者：
Anwar SL;Krech T;Hasemeier B;Schipper E;Schweitzer N;Vogel A;Kreipe H;Lehmann U
通讯作者：
Lehmann U
影响因子：
6.5
作者：
Choudhury, Aniruddha;Derkow, Katja;Mellstedt, Hakan
通讯作者：
Mellstedt, Hakan