生物钟与缺氧诱导因子在肿瘤领域的相关性
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摘要
生物钟是机体为适应周围环境,经过长期进化而来的内在适应性反应,它受外界环境(辐射、药物等)影响引起DNA损伤而使节律重新设置。肿瘤的发生、发展可改变机体微环境,近期越来越多研究表明肿瘤疾病进展与机体生物钟紊乱密切相关。本文通过对生物钟和缺氧诱导因子(hypoxia-induciblefactor,HIF)的结构、调控及表达角度分析,对缺氧及生物钟相关性进行综述性介绍,以期凭靶向调节生物钟来改善机体肿瘤疾病进展的研究提供参考,同时希望能促进时间生物学领域与更多其他领域形成交叉研究。
The circadian clocks are internal adaptive responses which are evolved to adapt to the surrounding environment for the organisms. They can be affected by the external environments(such as radiation, drugs, etc.) and cause DNA damages and reset the rhythms. The occurrence and development of tumors can change the microenvironment of the body. Recently, more and more studies have shown that the progression of tumor diseases is closely related to the disorder of circadian rhythms. In this review, we analyze the structures, regulations and expressions of circadian clocks and hypoxia inducible factors to summarize the correlation between them. Besides, we hope it can offer basic knowledge for further researches, a reference for experimental designs aiming to adjust the progressionsof neoplastic diseases by modulating the circadian rhythms, and provide a foundation to build interdisciplinary research networks.
The circadian clocks are internal adaptive responses which are evolved to adapt to the surrounding environment for the organisms. They can be affected by the external environments(such as radiation, drugs, etc.) and cause DNA damages and reset the rhythms. The occurrence and development of tumors can change the microenvironment of the body. Recently, more and more studies have shown that the progression of tumor diseases is closely related to the disorder of circadian rhythms. In this review, we analyze the structures, regulations and expressions of circadian clocks and hypoxia inducible factors to summarize the correlation between them. Besides, we hope it can offer basic knowledge for further researches, a reference for experimental designs aiming to adjust the progressionsof neoplastic diseases by modulating the circadian rhythms, and provide a foundation to build interdisciplinary research networks.
引文
1.Hunyor I,Cook KM.Models of intermittent hypoxia and obstructive sleep apnea:molecular pathways and their contribution to cancer[J].Am J Physiol Regul Integr Comp Physiol,2018,315(4):R669-R687.
2.Yu C,Yang SL,Fang X,et al.Hypoxia disrupts the expression levels of circadian rhythm genes in hepatocellular carcinoma[J].Mol Med Rep,2015,11(5):4002-4008.
3.Okabe T,Kumagai M,Nakajima Y,et al.The impact of HIF1alpha on the Per2 circadian rhythm in renal cancer cell lines[J].PLoS One,2014,9(10):e109693.
4.Loudon,AS.Circadian biology:a 2.5 billion year old clock[J].Curr Biol,2012,22(14):R570-R571.
5.Bass J,Takahashi JS.Circadian integration of metabolism and energetics[J].Science,2010,330(6009):1349-1354.
6.Mills DB,Ward LM,Jones C,et al.Oxygen requirements of the earliest animals[J].Proc Natl Acad Sci U S A,2014,111(11):4168-4172.
7.Song X,Liu X,Chi W,et al.Hypoxia-induced resistance to cisplatin and doxorubicin in non-small cell lung cancer is inhibited by silencing of HIF-1alpha gene[J].Cancer Chemother Pharmacol,2006,58(6):776-784.
8.Fu L,Kettner NM.The circadian clock in cancer development and therapy[J].Prog Mol Biol Transl Sci,2013,119:221-282.
9.Wu Y,Tang D,Liu N,et al.Reciprocal regulation between the circadian clock and hypoxia signaling at the genome level in mammals[J].Cell Metab,2017,25(1):73-85.
10.Rey G,Reddy AB.Physiology.Rhythmic respiration[J].Science,2013,342(6158):570-571.
11.Takahashi JS.Transcriptional architecture of the mammalian circadian clock[J].Nat Rev Genet,2017,18(3):164-179.
12.Schibler U,Gotic I,Saini C,et al.Clock-talk:interactions between central and peripheral circadian oscillators in mammals[J].Cold Spring Harb Symp Quant Biol,2015,80:223-232.
13.Benirschke K.Chronobiology:biological timekeeping[J].J Hered,2004,95(1):91-92.
14.Buijs RM,Hermes MH,Kalsbeek A.The suprachiasmatic nucleusparaventricular nucleus interactions:a bridge to the neuroendocrine and autonomic nervous system[J].Prog Brain Res,1998,119:365-382.
15.Pelster B,Egg M.Multiplicity of hypoxia-inducible transcription factors and their connection to the circadian clock in the zebrafish[J].Physiol Biochem Zool,2015,88(2):146-157.
16.Tang X,Guo D,Lin C,et al.Upregulation of the gene expression of CLOCK is correlated with hypoxia-inducible factor 1alpha in advanced varicose lesions[J].Mol Med Rep,2015,12(4):6164-6170.
17.Kumar H,Choi DK.Hy pox ia inducible factor pathway and physiological adaptation:a cell survival pathway?[J].Mediators Inflamm,2015,2015:584758.
18.Hahne M,Schumann P,Mursell M,et al.Unraveling the role of hypoxia-inducible factor(HIF)-1alpha and HIF-2alpha in the adaption process of human microvascular endothelial cells(HMEC-1)to hypoxia:redundant HIF-dependent regulation of macrophage migration inhibitory factor[J].Microvasc Res,2018,116:34-44.
19.Palazon A,Tyrakis PA,Macias D,et al.An HIF-1alpha/VEGF-A axis in cytotoxic T cells regulates tumor progression[J].Cancer Cell,2017,32(5):669-683.e5.
20.Scott CL,Walker DJ,Cwiklinski E,et al.Control of HIF-1{alpha}and vascular signaling in fetal lung involves cross talk between mTORC1and the FGF-10/FGFR2b/Spry2 air way branching periodicity clock[J].Am J Physiol Lung Cell Mol Physiol,2010,299(4):L455-L471.
21.Shah T,Krishnamachary B,Wildes F,et al.HIF isoforms have divergent effects on invasion,metastasis,metabolism and formation of lipid droplets[J].Oncotarget,2015,6(29):28104-28119.
22.Mole DR,Blancher C,Copley RR,et al.Genome-wide association of hypoxia-inducible factor(HIF)-1alpha and HIF-2alpha DNA binding with expression profiling of hypoxia-inducible transcripts[J].J Biol Chem,2009,284(25):16767-16775.
23.Fraisl P,Mazzone M,Schmidt T,et al.Regulation of angiogenesis by oxygen and metabolism[J].Dev Cell,2009,16(2):167-179.
24.Tanaka T,Wiesener M,Bernhardt W,et al.The human HIF(hypoxiainducible factor)-3alpha gene is a HIF-1 target gene and may modulate hypoxic gene induction[J].Biochem J,2009,424(1):143-151.
25.Makino Y,Kanopka A,Wilson WJ,et al.Inhibitory PAS domain protein(IPAS)is a hypoxia-inducible splicing variant of the hypoxia-inducible factor-3alpha locus[J].J Biol Chem,2002,277(36):32405-32408.
26.Hogenesch JB,Gu YZ,Jain S,et al.The basic-helix-loop-helixPAS orphan MOP3 forms transcriptionally active complexes with circadian and hypoxia factors[J].Proc Natl Acad Sci U S A,1998,95(10):5474-5479.
27.Weidemann A1,Johnson RS.Biology of HIF-1alpha[J].Cell Death Differ,2008,15(4):621-627.
28.Mu?oz E,Brewer M,Baler R.Circadian transcription.Thinking outside the E-Box[J].J Biol Chem,2002,277(39):36009-36017.
29.Joseph V,Mamet J,Lee F,et al.Prenatal hypoxia impairs circadian synchronisation and response of the biological clock to light in adult rats[J].J Physiol,2002,543(Pt 1):387-395.
30.Ghorbel MT,Coulson JM,Murphy D.Cross-talk between hypoxic and circadian pathways:cooperative roles for hypoxia-inducible factor1alpha and CLOCK in transcriptional activation of the vasopressin gene[J].Mol Cell Neurosci,2003,22(3):396-404.
31.Chilov D,Hofer T,Bauer C,et al.Hypoxia affects expression of circadian genes PER1 and CLOCK in mouse brain[J].FASEB J,2001,15(14):2613-2622.
32.Sato F,Bhawal UK,Yoshimura T,et al.DEC1 and DEC2 crosstalk between circadian rhythm and tumor progression[J].J Cancer,2016,7(2):153-159.
33.Sahar S,Zocchi L,Kinoshita C,et al.Regulation of BMAL1protein stability and circadian function by GSK3beta-mediated phosphorylation[J].PLoS One,2010,5(1):e8561.
34.Agostino PV,Harrington ME,Ralph MR,et al.Casein kinase-1-epsilon(CK1epsilon)and circadian photic responses in hamsters[J].Chronobiol Int,2009,26(1):126-133.
35.Kalousi A,Mylonis I,Politou AS,et al.Casein kinase 1 regulates human hypoxia-inducible factor HIF-1[J].J Cell Sci,2010,123(Pt17):2976-2986.
36.Kobayashi M,Morinibu A,Koyasu S,et al.A circadian clock gene,PER2,activates HIF-1 as an effector molecule for recruitment of HIF-1αto promoter regions of its downstream genes[J].FEBS J,2017,284(22):3804-3816.
37.Peek CB,Levine DC,Cedernaes J,et al.Circadian clock interaction with HIF1αmediates oxygenic metabolism and anaerobic glycolysis in skeletal muscle[J].Cell Metab,2017,25(1):86-92.
38.Adamovich Y,Ladeuix B,Golik M,et al.Rhythmic oxygen levels reset circadian clocks through HIF1α[J].Cell Metab,2017,25(1):93-101.
39.Grant WB.Re:“Night work and the risk of cancer among men”[J].Am J Epidemiol,2013,177(10):1165-1166.
2.Yu C,Yang SL,Fang X,et al.Hypoxia disrupts the expression levels of circadian rhythm genes in hepatocellular carcinoma[J].Mol Med Rep,2015,11(5):4002-4008.
3.Okabe T,Kumagai M,Nakajima Y,et al.The impact of HIF1alpha on the Per2 circadian rhythm in renal cancer cell lines[J].PLoS One,2014,9(10):e109693.
4.Loudon,AS.Circadian biology:a 2.5 billion year old clock[J].Curr Biol,2012,22(14):R570-R571.
5.Bass J,Takahashi JS.Circadian integration of metabolism and energetics[J].Science,2010,330(6009):1349-1354.
6.Mills DB,Ward LM,Jones C,et al.Oxygen requirements of the earliest animals[J].Proc Natl Acad Sci U S A,2014,111(11):4168-4172.
7.Song X,Liu X,Chi W,et al.Hypoxia-induced resistance to cisplatin and doxorubicin in non-small cell lung cancer is inhibited by silencing of HIF-1alpha gene[J].Cancer Chemother Pharmacol,2006,58(6):776-784.
8.Fu L,Kettner NM.The circadian clock in cancer development and therapy[J].Prog Mol Biol Transl Sci,2013,119:221-282.
9.Wu Y,Tang D,Liu N,et al.Reciprocal regulation between the circadian clock and hypoxia signaling at the genome level in mammals[J].Cell Metab,2017,25(1):73-85.
10.Rey G,Reddy AB.Physiology.Rhythmic respiration[J].Science,2013,342(6158):570-571.
11.Takahashi JS.Transcriptional architecture of the mammalian circadian clock[J].Nat Rev Genet,2017,18(3):164-179.
12.Schibler U,Gotic I,Saini C,et al.Clock-talk:interactions between central and peripheral circadian oscillators in mammals[J].Cold Spring Harb Symp Quant Biol,2015,80:223-232.
13.Benirschke K.Chronobiology:biological timekeeping[J].J Hered,2004,95(1):91-92.
14.Buijs RM,Hermes MH,Kalsbeek A.The suprachiasmatic nucleusparaventricular nucleus interactions:a bridge to the neuroendocrine and autonomic nervous system[J].Prog Brain Res,1998,119:365-382.
15.Pelster B,Egg M.Multiplicity of hypoxia-inducible transcription factors and their connection to the circadian clock in the zebrafish[J].Physiol Biochem Zool,2015,88(2):146-157.
16.Tang X,Guo D,Lin C,et al.Upregulation of the gene expression of CLOCK is correlated with hypoxia-inducible factor 1alpha in advanced varicose lesions[J].Mol Med Rep,2015,12(4):6164-6170.
17.Kumar H,Choi DK.Hy pox ia inducible factor pathway and physiological adaptation:a cell survival pathway?[J].Mediators Inflamm,2015,2015:584758.
18.Hahne M,Schumann P,Mursell M,et al.Unraveling the role of hypoxia-inducible factor(HIF)-1alpha and HIF-2alpha in the adaption process of human microvascular endothelial cells(HMEC-1)to hypoxia:redundant HIF-dependent regulation of macrophage migration inhibitory factor[J].Microvasc Res,2018,116:34-44.
19.Palazon A,Tyrakis PA,Macias D,et al.An HIF-1alpha/VEGF-A axis in cytotoxic T cells regulates tumor progression[J].Cancer Cell,2017,32(5):669-683.e5.
20.Scott CL,Walker DJ,Cwiklinski E,et al.Control of HIF-1{alpha}and vascular signaling in fetal lung involves cross talk between mTORC1and the FGF-10/FGFR2b/Spry2 air way branching periodicity clock[J].Am J Physiol Lung Cell Mol Physiol,2010,299(4):L455-L471.
21.Shah T,Krishnamachary B,Wildes F,et al.HIF isoforms have divergent effects on invasion,metastasis,metabolism and formation of lipid droplets[J].Oncotarget,2015,6(29):28104-28119.
22.Mole DR,Blancher C,Copley RR,et al.Genome-wide association of hypoxia-inducible factor(HIF)-1alpha and HIF-2alpha DNA binding with expression profiling of hypoxia-inducible transcripts[J].J Biol Chem,2009,284(25):16767-16775.
23.Fraisl P,Mazzone M,Schmidt T,et al.Regulation of angiogenesis by oxygen and metabolism[J].Dev Cell,2009,16(2):167-179.
24.Tanaka T,Wiesener M,Bernhardt W,et al.The human HIF(hypoxiainducible factor)-3alpha gene is a HIF-1 target gene and may modulate hypoxic gene induction[J].Biochem J,2009,424(1):143-151.
25.Makino Y,Kanopka A,Wilson WJ,et al.Inhibitory PAS domain protein(IPAS)is a hypoxia-inducible splicing variant of the hypoxia-inducible factor-3alpha locus[J].J Biol Chem,2002,277(36):32405-32408.
26.Hogenesch JB,Gu YZ,Jain S,et al.The basic-helix-loop-helixPAS orphan MOP3 forms transcriptionally active complexes with circadian and hypoxia factors[J].Proc Natl Acad Sci U S A,1998,95(10):5474-5479.
27.Weidemann A1,Johnson RS.Biology of HIF-1alpha[J].Cell Death Differ,2008,15(4):621-627.
28.Mu?oz E,Brewer M,Baler R.Circadian transcription.Thinking outside the E-Box[J].J Biol Chem,2002,277(39):36009-36017.
29.Joseph V,Mamet J,Lee F,et al.Prenatal hypoxia impairs circadian synchronisation and response of the biological clock to light in adult rats[J].J Physiol,2002,543(Pt 1):387-395.
30.Ghorbel MT,Coulson JM,Murphy D.Cross-talk between hypoxic and circadian pathways:cooperative roles for hypoxia-inducible factor1alpha and CLOCK in transcriptional activation of the vasopressin gene[J].Mol Cell Neurosci,2003,22(3):396-404.
31.Chilov D,Hofer T,Bauer C,et al.Hypoxia affects expression of circadian genes PER1 and CLOCK in mouse brain[J].FASEB J,2001,15(14):2613-2622.
32.Sato F,Bhawal UK,Yoshimura T,et al.DEC1 and DEC2 crosstalk between circadian rhythm and tumor progression[J].J Cancer,2016,7(2):153-159.
33.Sahar S,Zocchi L,Kinoshita C,et al.Regulation of BMAL1protein stability and circadian function by GSK3beta-mediated phosphorylation[J].PLoS One,2010,5(1):e8561.
34.Agostino PV,Harrington ME,Ralph MR,et al.Casein kinase-1-epsilon(CK1epsilon)and circadian photic responses in hamsters[J].Chronobiol Int,2009,26(1):126-133.
35.Kalousi A,Mylonis I,Politou AS,et al.Casein kinase 1 regulates human hypoxia-inducible factor HIF-1[J].J Cell Sci,2010,123(Pt17):2976-2986.
36.Kobayashi M,Morinibu A,Koyasu S,et al.A circadian clock gene,PER2,activates HIF-1 as an effector molecule for recruitment of HIF-1αto promoter regions of its downstream genes[J].FEBS J,2017,284(22):3804-3816.
37.Peek CB,Levine DC,Cedernaes J,et al.Circadian clock interaction with HIF1αmediates oxygenic metabolism and anaerobic glycolysis in skeletal muscle[J].Cell Metab,2017,25(1):86-92.
38.Adamovich Y,Ladeuix B,Golik M,et al.Rhythmic oxygen levels reset circadian clocks through HIF1α[J].Cell Metab,2017,25(1):93-101.
39.Grant WB.Re:“Night work and the risk of cancer among men”[J].Am J Epidemiol,2013,177(10):1165-1166.