ITPKA Gene Body Methylation Regulates Gene Expression and Serves as an Early Diagnostic Marker in Lung and Other Cancers.
ITPKA Gene Body Methylation Regulates Gene Expression and Serves as an Early Diagnostic Marker in Lung and Other Cancers.
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DOI：
10.1016/j.jtho.2016.05.010
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发表时间：
2016-09
期刊：
影响因子：
--
通讯作者：
Gazdar AF
中科院分区：
文献类型：
--
作者：
Wang YW;Ma X;Zhang YA;Wang MJ;Yatabe Y;Lam S;Girard L;Chen JY;Gazdar AF
尽管最近在癌症治疗方面取得了进展，但肺癌患者的总体5年生存率仍然很低。我们研究的目的是寻找用于肺癌患者早期诊断的新标志物。在原发性肺腺癌和细胞系中进行互补DNA微阵列分析以寻找差异表达的基因，然后进行体内和体外致瘤性测定以表征候选基因的致癌潜力。通过450 K甲基化阵列、亚硫酸氢盐测序和定量甲基化特异性聚合酶链反应分析基因体甲基化。还进行了癌症基因组图谱数据集的计算机模拟分析。三磷酸肌醇3-激酶A基因（ITPKA）是一种组织分布有限的激酶，被认为是一种潜在的癌基因。我们发现ITPKA表达在许多形式的癌症中上调，包括肺癌和乳腺癌，并且过表达的ITPKA有助于肿瘤发生。我们还证明，ITPKA的表达是由ITPKA基因体的表观遗传DNA甲基化通过调节SP1转录因子与ITPKA启动子的结合来调节的。ITPKA基因体在大多数正常组织中显示低水平或无甲基化，但在恶性肿瘤中显著甲基化。在肺癌中，ITPKA基因体甲基化首先出现在原位癌阶段，并在浸润后进行性增加。ITPKA是一种潜在的癌基因，在大多数肿瘤中过表达，其过表达促进肿瘤的发生。ITPKA基因体甲基化调节其表达，因此可作为早期癌症检测的新的和潜在的生物标志物。
Despite recent advances in cancer therapy, the overall 5-year survival rate of patients with lung cancer remains low. The aim of our study was to search for novel markers for early diagnosis in patients with lung cancer. Complementary DNA microarray analysis was performed in primary lung adenocarcinomas and cell lines to search for differentially expressed genes, followed by in vivo and in vitro tumorigenic assays to characterize the oncogenic potential of the candidate genes. Gene body methylation was analyzed by 450K methylation array, bisulfite sequencing, and quantitative methylation-specific polymerase chain reaction assays. In silico analysis of The Cancer Genome Atlas data set was also performed. Inositol-trisphosphate 3-kinase A gene (ITPKA), a kinase with limited tissue distribution, was identified as a potential oncogene. We showed that ITPKA expression is up-regulated in many forms of cancers, including lung and breast cancers, and that overexpressed ITPKA contributes to tumorigenesis. We also demonstrated that ITPKA expression is regulated by epigenetic DNA methylation of ITPKA gene body through modulation of the binding of SP1 transcription factor to the ITPKA promoter. ITPKA gene body displayed low or absent levels of methylation in most normal tissue but was significantly methylated in malignant tumors. In lung cancer, ITPKA gene body methylation first appeared at the in situ carcinoma stage and progressively increased after invasion. ITPKA is a potential oncogene that it is overexpressed in most tumors, and its overexpression promotes tumorigenesis. ITPKA gene body methylation regulates its expression and thus serves as a novel and potential biomarker for early cancer detection.
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DOI：
10.1073/pnas.1215145110
发表时间：
2013-04-09
影响因子：
11.1
作者：
Schroeder, Diane I.;Blair, John D.;LaSalle, Janine M.
通讯作者：
LaSalle, Janine M.
DOI：
10.1016/j.bbrc.2008.05.101
发表时间：
2008-08-08
影响因子：
3.1
作者：
Liu, Lei;Liao, Guo-qing;Yin, Yan-hui
通讯作者：
Yin, Yan-hui
影响因子：
3.5
作者：
Kim, J;Kollhoff, A;Stubbs, L
通讯作者：
Stubbs, L
影响因子：
11.5
作者：
Nakagawa, K;Noguchi, Y;Nakayama, E
通讯作者：
Nakayama, E
影响因子：
4.1
作者：
VANWEYENBERG, V;COMMUNI, D;ERNEUX, C
通讯作者：
ERNEUX, C