DEC1 and DEC2 Crosstalk between Circadian Rhythm and Tumor Progression.
DEC1 and DEC2 Crosstalk between Circadian Rhythm and Tumor Progression.
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DEC1 和 DEC2 昼夜节律与肿瘤进展之间的串扰。
DOI：
10.7150/jca.13748
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发表时间：
2016
影响因子：
3.9
通讯作者：
Muragaki Y
中科院分区：
文献类型：
--
作者：
Sato F;Bhawal UK;Yoshimura T;Muragaki Y
生物钟基因是昼夜节律的主要调节因子，参与肿瘤的进展。我们已经发现，时钟基因碱性螺旋-环-螺旋（BHLH）转录因子，分化胚胎软骨细胞基因1（DEC1/BHLHE40/Sharp2/Stra13）和DEC2（BHLHE41/Sharp1）在昼夜节律，细胞增殖，凋亡，缺氧反应，各种应激和肿瘤细胞的上皮间质转化（EMT）中发挥重要作用。各种应激，如暴露于转化生长因子-β（TGF-β）、缺氧、细胞因子、无血清和抗肿瘤药物，都会影响DEC1和DEC2的表达。DEC 1和DEC 2表达的增加或减少调节肿瘤进展。然而，DEC1和DEC2在肿瘤进展中具有相反的作用，其背后的原因尚不清楚。我们发现DEC2在植入的小鼠肉瘤细胞中具有昼夜节律表达，表明DEC2在昼夜节律下调节肿瘤进展。此外，我们发现DEC1和DEC2在肿瘤进展中通过正反馈或负反馈系统调节靶基因。我们认为DEC1和DEC2在肿瘤进展中起着加速器或制动器的作用。本文就DEC1和DEC2基因在肿瘤发生发展中的作用作一综述。
Clock genes, major regulators of circadian rhythm, are involved in tumor progression. We have shown that clock genes basic helix-loop-helix (BHLH) transcription factors, differentiated embryonic chondrocyte gene 1 (DEC1/BHLHE40/Sharp2/Stra13) and DEC2 (BHLHE41/Sharp1) play important roles in circadian rhythm, cell proliferation, apoptosis, hypoxia response, various stresses, and epithelial-to-mesenchymal transition (EMT) of tumor cells. Various stresses, such as exposure to transforming growth factor-beta (TGF-β), hypoxia, cytokines, serum-free, and anti-tumor drugs affect DEC1 and DEC2 expression. An increased or decreased expression of DEC1 and DEC2 regulated tumor progression. However, DEC1 and DEC2 have opposite effects in tumor progression, where the reason behind remains unclear. We found that DEC2 has circadian expression in implanted mouse sarcoma cells, suggesting that DEC2 regulates tumor progression under circadian rhythm. In addition to that, we showed that DEC1 and DEC2 regulate target genes via positive or negative feedback system in tumor progression. We propose that DEC1 and DEC2 act as an accelerator or a brake in tumor progression. In this review, we summarize current progress of knowledge in the function of DEC1 and DEC2 genes in tumor progression.