Preservation of circadian rhythm in hepatocellular cancer.
Preservation of circadian rhythm in hepatocellular cancer.
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DOI：
10.1016/j.jbc.2023.105251
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发表时间：
2023-10
影响因子：
4.8
通讯作者：
Sancar, Aziz
中科院分区：
文献类型：
--
作者：
Yang, Yanyan;Abdo, Ashraf N.;Kawara, Hiroaki;Selby, Christopher P.;Sancar, Aziz
昼夜节律在细胞水平上由分子钟控制，该分子钟由参与转录-翻译-降解反馈回路的若干基因/蛋白质组成。这些核心时钟蛋白调节数千个组织特异性基因。关于肿瘤组织中的昼夜节律控制，迄今为止的报道已经证明了肿瘤模型和培养的肿瘤细胞中的异常昼夜节律功能。我们通过分析肝癌小鼠模型中全基因组的昼夜节律性来扩展这些研究，在该模型中，用二乙基亚硝胺治疗15天的小鼠在6个月内发展为肝肿瘤。我们在24小时周期内每2小时向荷瘤小鼠和对照无肿瘤小鼠注射顺铂;每次注射后2小时处死小鼠，并通过XR-Seq（切除修复测序）测定法测量基因表达。在健康肝脏和肿瘤中观察到几个核心时钟基因的节律性表达，肿瘤中的时钟基因表现出典型的稳健幅度和适度的相位提前。有趣的是，尽管正常肝细胞和肝癌细胞表达了相当数量的具有昼夜节律的基因（时钟控制基因），但正常细胞和癌细胞中的节律基因之间只有约10%的重叠。“仅在肿瘤中有节律”基因主要在白天表现出峰值表达时间，与健康肝脏中更常见的黎明前和黄昏前表达时间形成对比。随着时间的推移，肿瘤和健康肝脏中基因的差异表达可能为更有效的抗癌药物治疗提供了机会，作为治疗时间的函数。
Circadian rhythms are controlled at the cellular level by a molecular clock consisting of several genes/proteins engaged in a transcription–translation–degradation feedback loop. These core clock proteins regulate thousands of tissue-specific genes. Regarding circadian control in neoplastic tissues, reports to date have demonstrated anomalous circadian function in tumor models and cultured tumor cells. We have extended these studies by analyzing circadian rhythmicity genome-wide in a mouse model of liver cancer, in which mice treated with diethylnitrosamine at 15 days develop liver tumors by 6 months. We injected tumor-bearing and control tumor-free mice with cisplatin every 2 h over a 24-h cycle; 2 h after each injection mice were sacrificed and gene expression was measured by XR-Seq (excision repair sequencing) assay. Rhythmic expression of several core clock genes was observed in both healthy liver and tumor, with clock genes in tumor exhibiting typically robust amplitudes and a modest phase advance. Interestingly, although normal hepatic cells and hepatoma cancer cells expressed a comparable number of genes with circadian rhythmicity (clock-controlled genes), there was only about 10% overlap between the rhythmic genes in normal and cancerous cells. “Rhythmic in tumor only” genes exhibited peak expression times mainly in daytime hours, in contrast to the more common pre-dawn and pre-dusk expression times seen in healthy livers. Differential expression of genes in tumors and healthy livers across time may present an opportunity for more efficient anticancer drug treatment as a function of treatment time.
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影响因子：
64.5
作者：
Masri S;Papagiannakopoulos T;Kinouchi K;Liu Y;Cervantes M;Baldi P;Jacks T;Sassone-Corsi P
通讯作者：
Sassone-Corsi P
影响因子：
5.6
作者：
Giovannini C;Bolondi L;Gramantieri L
通讯作者：
Gramantieri L
影响因子：
5.5
作者：
Altman BJ
通讯作者：
Altman BJ
DOI：
10.1073/pnas.1614430113
发表时间：
2016-10-11
影响因子：
11.1
作者：
Hu, Jinchuan;Lieb, Jason D.;Adar, Sheera
通讯作者：
Adar, Sheera
DOI：
10.1007/s00018-018-2746-7
发表时间：
2018-07
期刊：
Cellular and molecular life sciences : CMLS
影响因子：
--
作者：
Moura DS;Campillo-Marcos I;Vázquez-Cedeira M;Lazo PA
通讯作者：
Lazo PA