Biological and clinical significance of epigenetic silencing of MARVELD1 gene in lung cancer.
Biological and clinical significance of epigenetic silencing of MARVELD1 gene in lung cancer.
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MARVELD1 基因表观遗传沉默在肺癌中的生物学和临床意义。
DOI：
10.1038/srep07545
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发表时间：
2014-12-18
影响因子：
4.6
通讯作者：
Li Y
中科院分区：
文献类型：
--
作者：
Shi M;Wang S;Yao Y;Li Y;Zhang H;Han F;Nie H;Su J;Wang Z;Yue L;Cao J;Li Y
在肿瘤发展的早期阶段，癌症的表观遗传沉默经常改变信号转导途径。癌症表观遗传学领域的最新进展为癌症的诊断和治疗带来了新的机会。我们之前证明了新鉴定的核因子MARVELD1在人体组织中广泛表达，但在多种癌症中被启动子甲基化下调。本研究旨在确定肺癌中MARVELD1基因沉默的生物学和临床意义。我们发现，MARVELD1表达的降低与肺癌的诊断组织病理学和恶性程度显著相关。肺癌细胞DNA超甲基化和组蛋白去乙酰化协同失活MARVELD1基因。此外，MARVELD1通过与NMD核心因子SMG1的相互作用调节无义介导的mRNA衰变（NMD）的效率。肺癌中MARVELD1水平的降低通过降低NMD复合物UPF1/SMG1与含mRNA的过早终止密码子（PTC-mRNA）之间的关联而降低NMD效率。结果表明，MARVELD1基因沉默是一种很有吸引力的肺癌诊断生物标志物，其表观遗传沉默与肺癌NMD通路的调控机制有关，可能是肿瘤发生所必需的。
Epigenetic silence in cancer frequently altered signal-transduction pathways during the early stages of tumor development. Recent progress in the field of cancer epigenetics has led to new opportunities for diagnosis and treatment of cancer. We previously demonstrated that novel identified nuclear factor MARVELD1 was widely expressed in human tissues, but down-regulated by promoter methylation in multiple cancers. This study was carried out to determine the biological and clinical significance of MARVELD1 gene silencing in lung cancer. Here, we found the reduced MARVELD1 expression significantly correlated with diagnostic histopathology and malignant degree of lung cancers. DNA hypermethylation and histone deacetylation synergistically inactivated MARVELD1 gene in lung cancer cells. Moreover, MARVELD1 modulated the efficiency of nonsense-mediated mRNA decay (NMD) through interaction with NMD core factor SMG1. The decreased MARVELD1 level in lung cancer reduces NMD efficiency through diminishing the association between NMD complex component UPF1/SMG1 and premature termination codons containing mRNA (PTC-mRNA). The results suggested that MARVELD1 silencing is an appealing diagnostic biomarker for lung cancer and epigenetic silencing of MARVELD1 gene links with the regulatory mechanism of NMD pathway in lung cancer, which may be required for tumorigenesis.
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影响因子：
15.8
作者：
Chan, Timothy A.;Glockner, Sabine;Yi, Joo Mi;Chen, Wei;Van Neste, Leander;Cope, Leslie;Herman, James G.;Velculescu, Victor;Schuebel, Kornel E.;Ahuja, Nita;Baylin, Stephen B.
通讯作者：
Baylin, Stephen B.
影响因子：
4.8
作者：
Chang, Yao-Fu;Chan, Wai-Kin;Wilkinson, Miles F.
通讯作者：
Wilkinson, Miles F.
DOI：
10.1038/nrm3454
发表时间：
2012-11
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
--
影响因子：
10.5
作者：
Sato, Hanae;Maquat, Lynne E.
通讯作者：
Maquat, Lynne E.
影响因子：
11.2
作者：
Cadieux, Benoit;Ching, Tsui-Ting;Costello, Joseph F.
通讯作者：
Costello, Joseph F.