Zinc Finger Protein CTCF Regulates Extracellular Matrix (ECM)-Related Gene Expression Associated With the Wnt Signaling Pathway in Gastric Cancer.
Zinc Finger Protein CTCF Regulates Extracellular Matrix (ECM)-Related Gene Expression Associated With the Wnt Signaling Pathway in Gastric Cancer.
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锌指蛋白 CTCF 调节胃癌中与 Wnt 信号通路相关的细胞外基质 (ECM) 相关基因表达
DOI：
10.3389/fonc.2020.625633
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发表时间：
2020
影响因子：
4.7
通讯作者：
Hu Y
中科院分区：
文献类型：
--
作者：
Liu C;Deng L;Lin J;Zhang J;Huang S;Zhao J;Jin P;Xu P;Ni P;Xu D;Ying L;Hu Y
胃癌(GC)是一种异质性疾病，是癌症相关死亡的主要原因。我们的目标是描述与临床相关的GC分子分类，包括异质性并提供有用的临床信息。我们结合不同的基因表达数据集，筛选出与细胞外基质(ECM)相关的7个基因签名，这也显示出对GC患者的显著预后价值。有趣的是，在这些ECM相关基因的启动子中发现了可能的CCCTC结合因子(CTCF)调控元件，并通过染色质免疫沉淀测序(ChIP-Seq)进行了证实。CTCF结合位点也与组蛋白激活标记重叠，表明直接调控。此外，CTCF还与Wnt信号通路相关。对高表达或低表达ECM相关基因的人GC细胞株进行比较，发现不同水平的肿瘤侵袭性，表明ECM相关基因具有促进肿瘤发展的功能。此外，CTCF在体外还调节COL1A1和COLA31的表达。沉默CTCF或COL1A1/COL1A3可显著抑制转移性胃癌细胞系BGC823的生长和迁移。总体而言，这种与ECM相关的7基因特征为GC患者的生存预测提供了新的见解。锌指蛋白CTCF调控细胞外基质相关基因，从而促进胃癌细胞的生长和迁移。
Gastric cancer (GC), a leading cause of cancer-related death, is a heterogeneous disease. We aim to describe clinically relevant molecular classifications of GC that incorporate heterogeneity and provide useful clinical information. We combined different gene expression datasets and filtered a 7-gene signature related to the extracellular matrix (ECM), which also exhibited significant prognostic value in GC patients. Interestingly, putative CCCTC-binding factor (CTCF) regulatory elements were identified within the promoters of these ECM-related genes and were confirmed by chromatin immunoprecipitation sequencing (ChIP-Seq). CTCF binding sites also overlapped with histone activation markers, indicating direct regulation. In addition, CTCF was also correlated with the Wnt signaling pathway. A comparison of human GC cell lines with high or low expression of ECM-related genes revealed different levels of tumor aggressiveness, suggesting the cancer development-promoting functions of ECM-related genes. Furthermore, CTCF regulated COL1A1 and COLA31 expression in vitro. Silencing CTCF or COL1A1/COL1A3 markedly inhibited cell growth and migration in the metastatic GC cell line BGC823. Collectively, this ECM-related 7-gene signature provides a novel insight for survival prediction among GC patients. The zinc finger protein CTCF regulates ECM-related genes, thereby promoting GC cell growth and migration.
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影响因子：
4.6
作者：
Bankhead P;Loughrey MB;Fernández JA;Dombrowski Y;McArt DG;Dunne PD;McQuaid S;Gray RT;Murray LJ;Coleman HG;James JA;Salto-Tellez M;Hamilton PW
通讯作者：
Hamilton PW
影响因子：
14.9
作者：
Ritchie ME;Phipson B;Wu D;Hu Y;Law CW;Shi W;Smyth GK
通讯作者：
Smyth GK
影响因子：
4.5
作者：
Ooi CH;Ivanova T;Wu J;Lee M;Tan IB;Tao J;Ward L;Koo JH;Gopalakrishnan V;Zhu Y;Cheng LL;Lee J;Rha SY;Chung HC;Ganesan K;So J;Soo KC;Lim D;Chan WH;Wong WK;Bowtell D;Yeoh KG;Grabsch H;Boussioutas A;Tan P
通讯作者：
Tan P
影响因子：
8.4
作者：
Ferro, Ana;Peleteiro, Barbara;Lunet, Nuno
通讯作者：
Lunet, Nuno
影响因子：
3.7
作者：
Gearing, Linden J.;Cumming, Helen E.;Hertzog, Paul J.
通讯作者：
Hertzog, Paul J.