Regulation of L1 expression and retrotransposition by melatonin and its receptor: implications for cancer risk associated with light exposure at night.
Regulation of L1 expression and retrotransposition by melatonin and its receptor: implications for cancer risk associated with light exposure at night.
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DOI：
10.1093/nar/gku503
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发表时间：
2014-07
影响因子：
14.9
通讯作者：
Belancio VP
中科院分区：
文献类型：
--
作者：
deHaro D;Kines KJ;Sokolowski M;Dauchy RT;Streva VA;Hill SM;Hanifin JP;Brainard GC;Blask DE;Belancio VP
长散布元件-1(L1)在许多人类恶性肿瘤中表达上调。L1可以通过插入突变和DNA双链断裂导致基因组不稳定，这两者都可能促进癌症。夜间光线暴露是一种最近被发现的致癌物质，它与倒班工人患癌症的风险增加有关。我们报道褪黑素受体1通过下调L1mRNA和ORF1蛋白来抑制培养细胞中L1的动员。褪黑素受体拮抗剂的加入以剂量依赖的方式取消了MT1对逆转座的影响。此外，在昼夜节律周期的不同时间采集的富含褪黑素但不缺乏褪黑素的人血，在组织分离的人类癌症异种移植的原位灌流过程中抑制内源性L1mRNA。在原位灌流期间补充外源性褪黑素或褪黑素受体拮抗剂的人血，建立了褪黑素对L1表达的受体介导的作用。结合组织培养和体内数据支持宿主的环境光暴露调节肿瘤中L1元件的表达。我们的数据表明，光诱导的对轮班工人褪黑激素产生的抑制可能会增加L1诱导的基因组中的基因组不稳定性，并表明L1活性与与昼夜节律中断相关的癌症发病率增加之间可能存在联系。
Expression of long interspersed element-1 (L1) is upregulated in many human malignancies. L1 can introduce genomic instability via insertional mutagenesis and DNA double-strand breaks, both of which may promote cancer. Light exposure at night, a recently recognized carcinogen, is associated with an increased risk of cancer in shift workers. We report that melatonin receptor 1 inhibits mobilization of L1 in cultured cells through downregulation of L1 mRNA and ORF1 protein. The addition of melatonin receptor antagonists abolishes the MT1 effect on retrotransposition in a dose-dependent manner. Furthermore, melatonin-rich, but not melatonin-poor, human blood collected at different times during the circadian cycle suppresses endogenous L1 mRNA during in situ perfusion of tissue-isolated xenografts of human cancer. Supplementation of human blood with exogenous melatonin or melatonin receptor antagonist during the in situ perfusion establishes a receptor-mediated action of melatonin on L1 expression. Combined tissue culture and in vivo data support that environmental light exposure of the host regulates expression of L1 elements in tumors. Our data imply that light-induced suppression of melatonin production in shift workers may increase L1-induced genomic instability in their genomes and suggest a possible connection between L1 activity and increased incidence of cancer associated with circadian disruption.
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影响因子：
7.5
作者：
Burgess, Rebecca C.;Misteli, Tom;Oberdoerffer, Philipp
通讯作者：
Oberdoerffer, Philipp
影响因子：
14.5
作者：
Belancio VP;Roy-Engel AM;Deininger PL
通讯作者：
Deininger PL
DOI：
10.4161/cc.21404
发表时间：
2012-09-15
期刊：
Cell cycle (Georgetown, Tex.)
影响因子：
--
作者：
Becker W
通讯作者：
Becker W
LINE-1 RNA剪接和对哺乳动物基因表达的影响。
影响因子：
14.9
作者：
Belancio, VP;Hedges, DJ;Deininger, P
通讯作者：
Deininger, P
影响因子：
14.9
作者：
Belancio VP;Roy-Engel AM;Pochampally RR;Deininger P
通讯作者：
Deininger P