EGR1 decreases the malignancy of human non-small cell lung carcinoma by regulating KRT18 expression.
EGR1 decreases the malignancy of human non-small cell lung carcinoma by regulating KRT18 expression.
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DOI：
10.1038/srep05416
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发表时间：
2014-07-03
影响因子：
4.6
通讯作者：
Gu Y
中科院分区：
文献类型：
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作者：
Zhang H;Chen X;Wang J;Guang W;Han W;Zhang H;Tan X;Gu Y
早期生长反应1 （Early growth response 1, EGR1）是一种多功能转录因子；EGR1在各种肿瘤中的正、负功能依赖于其调控的各种基因的综合功能。在这项研究中，我们观察了EGR1在非小细胞肺癌（NSCLC）中的作用，并确定了影响细胞命运和肿瘤发展的基因。各种实验表明，EGR1阻滞细胞迁移，抑制细胞迁移，诱导细胞凋亡。微阵列分析显示，随着EGR1的升高，CDKN1C、CDC27、PRKDC等100个基因的mRNA表达发生改变，参与了肿瘤进展的干预。生物信息学分析和启动子分析表明，EGR1结合位点位于KRT18（也称为CK18）的启动子中，KRT18可能有助于抑制NSCLC的发展。通过免疫组织化学方法研究了EGR1和KRT18在NSCLC临床病例中的表达水平，发现KRT18的蛋白表达与EGR1和淋巴结转移有显著相关性。这些结果共同证实了EGR1在非小细胞肺癌中作为肿瘤抑制因子发挥作用。本研究首次报道了KRT18的表达受EGR1的直接调控，并有助于降低NSCLC的恶性程度。
Early growth response 1 (EGR1) is a multifunctional transcription factor; Positive and negative functions of EGR1 in various tumors rely on the integrated functions of various genes it regulates. In this study, we observed the role of EGR1 in non-small-cell lung carcinoma (NSCLC) and identified genes that influence cell fate and tumor development. Various assays showed that EGR1 arrested cell mobility, inhibited migration, and induced apoptosis. Microarray analysis revealed that 100 genes, including CDKN1C, CDC27 and PRKDC, changed their mRNA expressions with the increase of EGR1 and contributed to intervention of tumor progression. Bioinformatics analysis and promoter analysis indicated that an EGR1 binding site was situated in the promoter of KRT18 (also named CK18) and KRT18 could assist in inhibition of NSCLC development. The expression level of EGR1 and KRT18 in NSCLC clinical cases was investigated by immunohistochemistry, in which the protein expression of KRT18 was found to be significantly associated with EGR1 and lymph node metastasis. The results collectively confirm that EGR1 functions as a tumor suppressor in NSCLC. This study is the first to report KRT18 expression is directly regulated by EGR1, and contributes to decrease malignancy of NSCLC.
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影响因子：
--
作者：
Lv, Haitao;Liu, Lian;Chen, Xi
通讯作者：
Chen, Xi
DOI：
10.1152/ajplung.00265.2007
发表时间：
2007-11-01
影响因子：
4.9
作者：
Ngiam, Nicola;Post, Martin;Kavanagh, Brian P.
通讯作者：
Kavanagh, Brian P.
影响因子：
4.4
作者：
Saberi, Samaneh;Douraghi, Masoumeh;Mohammadi, Marjan
通讯作者：
Mohammadi, Marjan
影响因子：
14.9
作者：
Huang DW;Sherman BT;Tan Q;Kir J;Liu D;Bryant D;Guo Y;Stephens R;Baseler MW;Lane HC;Lempicki RA
通讯作者：
Lempicki RA
DOI：
10.2217/fon.09.67
发表时间：
2009-09
期刊：
Future oncology (London, England)
影响因子：
--
作者：
Gitenay D;Baron VT
通讯作者：
Baron VT