Egr1在肝癌中的研究进展

doi:10.11904/j.issn.1002-3070.2022.05.008

摘要/Abstract

摘要： 肝癌是全球常见的恶性肿瘤,大多肝癌患者确诊时已处于中晚期。早期生长反应因子1(Egr1)是一种转录因子,在肝损伤期间被诱导,调控细胞增殖、肝损伤和修复过程中相关基因的表达,并且Egr1缺乏会延迟肝再生过程。最近的研究强调了Egr1在肝癌发生发展及治疗方面的双重作用。本文综述了Egr1在肝癌发生发展及治疗中可能的作用,并详细分析了Egr1参与的复杂信号途径,为临床疗效预测和发现新的治疗靶点提供参考。

关键词: 早期生长反应因子1, 肝癌, 发生发展, 治疗

Abstract: Liver cancer is a common malignant tumor in the world.Most patients with liver cancer were in the middle and late stages when diagnosed.Early growth response factor 1(Egr1)is a transcription factor that is induced during liver injury and regulates the expression of genes involved in cell proliferation,involved in cell proliferation and the role of Egr1 in liver injury and repair,and the lack of Egr1 will delay the process of liver regeneration.Recent studies have emphasized the dual role of Egr1 in the occurrence,development and treatment of liver cancer,thus affecting the progress of liver cancer.This article reviews the possible role of Egr1 in the occurrence,development and treatment of liver cancer,and analyzes in details the complex signal pathways involved by Egr1,so as to provide reference for clinical efficacy prediction and discovery of new therapeutic targets.

Key words: Egr1, Liver cancer, Occurrence and development, Treatment

中图分类号:

R735.7

孙兴璐, 陈彻. Egr1在肝癌中的研究进展[J]. 实用肿瘤学杂志, 2022, 36(5): 435-439.

SUN Xinglu, CHEN Che. Research progress of Egr1 in liver cancer[J]. Journal of Practical Oncology, 2022, 36(5): 435-439.

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链接本文: http://journal09.magtechjournal.com/Jwk3_syzlxzz/CN/10.11904/j.issn.1002-3070.2022.05.008

http://journal09.magtechjournal.com/Jwk3_syzlxzz/CN/Y2022/V36/I5/435

参考文献

1 Sung H,Ferlay J,Siegel RL,et al.Global cancer statistics 2020:globocan estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J].CA Cancer Clin,2021,71(3):209-249.
2 Wang B,Guo H,Yu H,et al.The role of the transcription factor EGR1 in cancer[J].Front Oncol,2021,11:642547.
3 Marignol L,Coffey M,Hollywood D,et al.Radiation to control transgene expression in tumors[J].Cancer Biol Ther,2007,6(7):10-12.
4 Bhattacharyya S,Fang F,Tourtellotte W,et al.Egr1:new conductor for the tissue repair orchestra directs harmony(regeneration)or cacophony(fibrosis)[J].Pathol,2013,229(2):86-97.
5 Li TT,Liu MR,Pei DS.Friend or foe,the role of Egr1 in cancer[J].Med Oncol,2019,37(12):7.
6 Duclot F,Kabbaj M.The role of early growth response 1(Egr1)in brain plasticity and neuropsychiatric disorders[J].Front Behav Neurosci,2017,6(5);11:35.
7 Swirnoff AH,Apel ED,Svaren J,et al.Nab1,a corepressor of NGFI-A(Egr1),contains an active transcriptional repression domain[J].Mol Cell Biol,1998,18(1):12-24.
8 Sevetson BR,Svaren J,Milbrandt J.A novel activation function for NAB proteins in EGR dependent transcription of the luteinizing hormone beta gene[J].Biol Chem,2000,275(13):49-57.
9 Kang HS,Ock J,Lee HJ,et al.Early growth response protein 1 upregulation and nuclear translocation by 2'-benzoyloxycinnamaldehyde induces prostate cancer cell death[J].Cancer Lett,2013,329(2):17-27.
10 Choi EJ,Yoo NJ,Kim MS,et al.Putative tumor suppressor genes Egr1 and BRSK1 are mutated in gastric and colo-rectal cancers[J].Oncology,2016,91(5):289-294.
11 Sun M,Nie FQ,Zang C,et al.The pseudogene DUXAP8 promotes non-small-cell lung cancer cell proliferation and invasion by epigenetically silencing EGR1 and RHOB[J].Mol Ther,2017,25(3):739-751.
12 Bi JG,Zheng JF,Li Q,et al.MicroRNA-181a-5p suppresses cell proliferation by targeting Egr1 and inhibiting Egr1/TGF-β/Smad pathway in hepatocellular carcinoma[J].Int Biochem Cell Biol,2019,106(1):107-116.
13 Gong D,Zeng Z,Yi F,et al.Inhibition of histone deacetylase 11 promotes human liver cancer cell apoptosis[J].Am Transl Res,2019,11(2):983-990.
14 Inoue K,Fry EA.Tumor suppression by the EGR1,DMP1,ARF,p53,and PTEN Network[J].Cancer Invest,2018,36(9/10):520-536.
15 Shin DY,Kim GY,Kim ND,et al.Induction of apoptosis by pectenotoxin-2 is mediated with the induction of DR4/DR5,Egr1 and NAG-1,activation of caspases and modulation of the Bcl-2 family in p53 deficient Hep3B hepatocellular carcinoma cells[J].Oncol Rep,2008,19(2):17-26.
16 Baek SJ,Kim JS,Nixon JB,et al.Expression of NAG-1,a transforming growth factorbeta superfamily member,by troglitazone requires the early growth response gene Egr1[J].Biol Chem,2004,279(8):83-92.
17 Chintharlapalli S,Papineni S,Baek SJ,et al.1,1-Bis(3'-indolyl)-1-(p-substitutedphenyl)methanes are peroxisome proliferator-activated receptor gamma agonists but decrease HCT-116 colon cancer cell survival through receptor independent activation of early growth response-1 and nonsteroidal anti-inflammatory drug-activated gene-1[J].Mol Pharmacol,2005,68(6):82-92.
18 Gong D,Zeng Z,Yi F,et al.Inhibition of histone deacetylase 11 promotes human liver cancer cell apoptosis[J].Am Transl Res,2019,11(2):983-990.
19 Ao H,Liu B,Li H,et al.Egr1 mediates retinal vascular dysfunction in diabetes mellitus via promoting p53 transcription[J].Cell Mol Med,2019,23(5):3345-3356.
20 Liedtke C,Trautwein C.The role of TNF and Fas dependent signaling in animal models of inflammatory liver injury and liver cancer[J].Eur Cell Biol,2012,91(6/7):582-589.
21 Jing Z,Ye X,Ma X,et al.SNGH16 regulates cell autophagy to promote sorafenib resistance through suppressing miR-23b-3p via sponging Egr1 in hepatocellular carcinoma[J].Cancer Med,2020,9(12):4324-4338.
22 Oliveto S,Mancino M,Manfrini N,et al.Role of microRNAs in translation regulation and cancer[J].World Biol Chem,2017,8(1):45-56.
23 Zhang L,Ren R,Yang X,et al.Oncogenic role of early growth response-1 in liver cancer through the regulation of the microRNA-675/sestrin 3 and the Wnt/β-catenin signaling pathway[J].Bioengineered,2021,12(1):5305-5322.
24 Li H,Li J,Jia S,et al.miR675 upregulates long noncoding RNA H19 through activating Egr1 in human liver cancer[J].Oncotarget,2015,6(11):58-84.
25 Bellam N,Pasche B.Tgf-beta signaling alterations and colon cancer[J].Cancer Treat Res,2010,155:85-103.
26 Matsuzaki K.Smad phosphoisoform signaling specificity:the right place at the right time[J].Carcinogenesis,2011,32(11):78-88.
27 Gilliam DT,Menon V,Bretz NP,et al.The CD24 surface antigen in neural development and disease[J].Neurobiol Dis,2017,99(3):133-144.
28 Li L,Chen J,Ge C,et al.CD24 isoform a promtes cell proliferation,migration and invasion and is downregulated by EGR1 in hepatocellular carcinoma[J].Onco Targets Ther,2019,12(2):1705-1716.
29 He S,Zhong Y,Shuai C,et al.Tumor suppressor NGX6 inhibits the growth and metastasis of multiple cancers[J].Tumour Biol,2016,37(5):5751-5760.
30 García-Vilas JA,Medina Má.Updates on the hepatocyte growth factor/c-Met axis in hepatocellular carcinoma and its therapeutic implications[J].World Gastroenterol,2018,24(33):3695-3708.
31 Zhang YW,Su Y,Volpert OV,et al.Hepatocyte growth factor/scatter factor mediates angiogenesis through positive VEGF and negative thrombospondin 1 regulation[J].Proc Natl Acad Sci U S A,2003,100(22):12718-12723.
32 Lee KH,Kim JR.Hepatocyte growth factor induced up-regulations of VEGF through Egr1 in hepatocellular carcinoma cells[J].Clin Exp Metastasis,2009,26(7):85-92.
33 He S,Zhong Y,Shuai C,et al.Tumor suppressor NGX6 inhibits the growth and metastasis of multiple cancers[J].Tumour Biol,2016,37(5):51-60.
34 Liu M,Wang X,Peng Y,et al.Egr1 regulates the transcription of NGX6 gene through a Sp1/Egr1 overlapping site in the promoter[J].BMC Mol Biol,2014,16(7):15:14.
35 Chen M,Wei L,Law CT,et al.RNA N6-methyladenosine methyltransferase-like 3 promotes liver cancer progression through YTHDF2-dependent posttranscriptional silencing of SOCS2[J].Hepatology,2018,67(6):2254-2270.
36 Lei T,Zhu X,Zhu K,et al.EGR1-induced up-regulation of lncRNA FO-D2-AS1 promotes the progression of hepatocellular carcinoma via epigenetically silencing DKK1 and activating wnt/β-catenin signaling pathway[J].Cancer Biol Ther,2019,20(7):1007-1016.
37 Zhang L,Ren R,Yang X,et al.Oncogenic role of early growth response-1 in liver cancer through the regulation of the microRNA-675/sestrin 3 and the Wnt/β-catenin signaling pathway[J].Bioengineered,2021,12(1):5305-5322.
38 Li X,Yu J,Brock MV,et al.Epigenetic silencing of BCL6B inactivates p53 signaling and causes human hepatocellular carcinoma cell resist to 5-FU[J].Oncotarget,2015,6(13):11547-11560.
39 Lin M,Huang J,Zhang J,et al.The therapeutic effect of PEI-Mn_0.5Zn_0.5Fe₂O₄ nanoparticles/pEgr1-HSV-TK/GCV associated with radiation and magnet-induced heating on hepatoma[J].Nanoscale,2013,5(3):991-1000.
40 Mei Lin,Zhang DS,Huang JX,et al.An evaluation on transfection efficiency of pHRE-Egr1-EGFP in hepatocellular carcinoma cells bel-7402 mediated by PEI-MZF-NPs[J].Nanomater,2011,23(1):242-248.
41 Hallahan DE,Mauceri HJ,Seung LP,et al.Spatial and temporal control of gene therapy using ionizing radiation[J].Nat Med,1995,1(8):86-91.
42 Liu Y,Wu MC,Qian GX.The experimental study of anti-human AFP variant Mc-Ab in radioimmuno-detection and radioimmuno-therapy of human hepatocellular carcinoma model in nude mice[J].Zhonghua Wai Ke Za Zhi,1994,32(11):650-653.
43 Loutski M,Remold-O'Donnell E,Roumiantsev AG,et al.Regulation of anti-tumor activity using monoclonal anti-bodies to alpha-fetoprotein receptor and after immunization with this protein[J].Russ Immunol,2001,6(3):257-264.
44 Lin M.Radio nuclide immune albumin nanospheres(¹³¹I-antiAFPMcAb-GCV-BSA-NPs):preparation and hepatoma targeting in vitro and in vivo[J].ACP,2016,91:42198.
45 Lin M,Huang J,Jiang X,et al.A combination hepatom a targeted therapy based on nanotechnology:pHRE-Egr1-HSV-TK/¹³¹I-antiAFPMc-Ab-GCV/MFH[J].Sci Rep,2016,6:33524.
46 Trusolino L,Bertotti A,Comoglio PM.MET signalling:principles and functions in development,organ regeneration and cancer[J].Nat Rev Mol Cell Biol,2010,11(12):34-48.
47 Bouattour M,Raymond E,Qin S,et al.Recent developments of c-Met as a therapeutic target in hepatocellular carcinoma[J].Hepatology,2018,67(3):1132-1149.
48 Chen HA,Kuo TC,Tseng CF,et al.Angiopoietin-like protein 1 antagonizes MET receptor activity to repress sorafenib resistance and cancer stemness in hepatocellular carcinoma[J].Hepatology,2016,64(5):1637-1651.
49 Xiang QF,Zhan MX,Li Y,et al.Activation of MET promotes resistance to sorafenib in hepatocellular carcinoma cells via the AKT/ERK1/2-EGR1 pathway[J].Artif Cells Nanomed Biotechnol,2019,47(1):83-89.

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