Sprouty4 is epigenetically upregulated in human colorectal cancer.
Sprouty4 is epigenetically upregulated in human colorectal cancer.
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DOI：
10.1080/15592294.2022.2145068
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发表时间：
2023-12
期刊：
影响因子：
3.7
通讯作者：
Khare, Sharad
中科院分区：
文献类型：
--
作者：
Stuckel, Alexei J.;Zengb, Shuai;Lyub, Zhen;Zhang, Wei;Zhang, Xu;Dougherty, Urszula;Mustafi, Reba;Khare, Tripti;Zhang, Qiong;Joshi, Trupti;Bissonnette, Marc;Khare, Sharad
Sputy4（SPRY4）经常被报道为肿瘤抑制因子，因此在各种癌症中下调。我们首次报道了SPRY4在结直肠癌（CRC）中的表观遗传上调。在这项研究中，我们探索了CRC细胞和患者样本中SPRY4的DNA甲基化和羟甲基化水平，并将这些发现与mRNA和蛋白质表达水平相关联。使用组合的亚硫酸氢盐限制性分析评估SPRY4启动子区域内的三个位点在CRC中的5mC水平。此外，在CRC患者中测量SPRY 4内的羟甲基化水平。最后，从多个高通量数据库（如Gene Expression Omnibus和The Cancer Genome Atlas）中提取CRC患者的DNA甲基化和mRNA表达数据。SPRY4启动子甲基化水平的体外和计算机分析清楚地表明，远端启动子区域在CRC患者中经历低甲基化，并与表达增加相关。此外，在CRC患者中发现SPRY4编码区基因体羟甲基化降低和基因体甲基化增加，并与表达增加相关。SPRY4在CRC中通过基因体内的启动子低甲基化和高甲基化表观遗传上调，这保证了未来对这种已建立的肿瘤抑制因子的非典型作用的研究。SPRY4基因在结直肠癌中表达增加SPRY4启动子DNA甲基化缺失，基因体在结直肠癌中获得DNA甲基化SPRY4基因体DNA羟甲基化缺失
Sprouty4 (SPRY4) has been frequently reported as a tumor suppressor and is therefore downregulated in various cancers. For the first time, we report that SPRY4 is epigenetically upregulated in colorectal cancer (CRC). In this study, we explored DNA methylation and hydroxymethylation levels of SPRY4 in CRC cells and patient samples and correlated these findings with mRNA and protein expression levels. Three loci within the promoter region of SPRY4 were evaluated for 5mC levels in CRC using the combined bisulfite restriction analysis. In addition, hydroxymethylation levels within SPRY4 were measured in CRC patients. Lastly, DNA methylation and mRNA expression data were extracted from CRC patients in multiple high-throughput data repositories like Gene Expression Omnibus and The Cancer Genome Atlas. Combined in vitro and in silico analysis of promoter methylation levels of SPRY4 clearly demonstrates that the distal promoter region undergoes hypomethylation in CRC patients and is associated with increased expression. Moreover, a decrease in gene body hydroxymethylation and an increase in gene body methylation within the coding region of SPRY4 were found in CRC patients and correlated with increased expression. SPRY4 is epigenetically upregulated in CRC by promoter hypomethylation and hypermethylation within the gene body that warrants future investigation of atypical roles of this established tumor suppressor. SPRY4 gene expression is increased in colorectal cancer The SPRY4 promoter loses DNA methylation, and the gene body gains DNA methylation in colorectal cancer The gene body of SPRY4 loses DNA hydroxymethylation
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影响因子：
5.8
作者：
Jing H;Liaw L;Friesel R;Vary C;Hua S;Yang X
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影响因子：
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DOI：
10.1158/1078-0432.ccr-15-3140
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2017-01-15
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DOI：
10.18632/aging.202859
发表时间：
2021-04-20
期刊：
Aging
影响因子：
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作者：
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影响因子：
14.9
作者：
Plotnik JP;Budka JA;Ferris MW;Hollenhorst PC
通讯作者：
Hollenhorst PC