AIM2在肿瘤中的研究进展

doi:10.11904/j.issn.1002-3070.2017.02.016

摘要/Abstract

摘要： 黑色素瘤缺乏因子(Absent in melanoma 2,AIM2),作为一种细胞内DNA感受器,能够感受到DNA病毒或细菌感染时释放到细胞浆的dsDNA,经ASC产生炎症复合体,进而活化Caspase-1,引起炎症因子IL-1β和IL-18的成熟和分泌,或引起Pyroptosis样细胞死亡,因此AIM2在固有免疫应答中发挥重要作用。近年的研究显示,AIM2能影响肿瘤的发生与发展,在肝癌、乳腺癌中表现为抑癌因子,抑制肿瘤的进展;在宫颈癌、口腔鳞状细胞癌中却表现出致癌效应,促进肿瘤的发展。这些研究结果对恶性肿瘤的诊断及预后起到帮助作用。

关键词: AIM2, 恶性肿瘤, 炎症小体

Abstract: Absent in melanoma 2(AIM2),as a cytoplasmic DNA sensor,can perceive the cytoplasmic dsDNA which released by the cells infected with DNA virus or bacteria.AIM2 will be raised by Apoptosis-associated speck-like protein containing a CARD to produce inflammation complex,activate of Caspase-1,promote the maturation,and secretion of IL-1β and IL-18,or lead to pyroptosis.AIM2 plays an importation role in initiating immunity.Recent research shows that AIM2 has an influence on the occurrence and progress in tumor,it acts as a tumor suppressor and inhibits tumor progression in liver and breast carcinoma;However,AIM2 shows the carcinogenic effect of promoting tumor development on cervical carcinoma and oral squamous cell carcinoma.These results contribute to the diagnosis and prognosis of malignant tumor.

Key words: AIM2, Malignant tumor, Inflammasome

中图分类号:

郝立肖(综述), 张云艳(审校). AIM2在肿瘤中的研究进展[J]. 实用肿瘤学杂志, 2017, 31(2): 175-178.

HAO Lixiao,ZHANG Yunyan. Research progress of AIM2 in tumor[J]. PRACTICAL ONCOLOGY JOURNAL, 2017, 31(2): 175-178.

参考文献

1 DeYoung KL,Ray ME,Su YA,et al.Cloning a novel member of the human interferon-inducible gene family associated with control of tumorigenicity in a model of human melanoma[J].Oncogene,1997,15(4):453-457.
2 Ma X,Guo P,Qiu Y,et al.Loss of AIM2 expression promotes hepatocarcinoma progression through activation of mTOR-S6K1 pathway[J].Oncotarget,2016,7(24):36185-36197.
3 Ponomareva L,Liu H,Duan X,et al.AIM2,an IFN-inducible cytosolic DNA sensor,in the development of benign prostate hyperplasia and prostate cancer[J].Mol Cancer Res,2013,11(10):1193-1202.
4 Chen IF,Ou-Yang F,Hung JY,et al.AIM2 suppresses human breast cancer cell proliferation in vitro and mammary tumor growth in a mouse model[J].Mol Cancer Ther,2006,5(1):1-7.
5 Liu ZY,Yi J,Liu FE.The molecular mechanism of breast cancer cell apoptosis induction by absent in melanoma(AIM2)[J].Int J Clin Exp Med,2015,8(9):14750-14758.
6 Wilson JE,Petrucelli AS,Chen L,et al.Inflammasome-independent role of AIM2 in suppressing colon tumorigenesis via DNA-PK and Akt[J].Nat Med,2015,21(8):906-913.
7 Man SM,Zhu Q,Zhu L,et al.Critical role for the DNA sensor AIM2 in stem cell proliferation and cancer[J].Cell,2015,162(1):45-58.
8 Roberts TL,Idris A,Dunn JA,et al.HIN-200 proteins regulate caspase activation in response to foreign cytoplasmic DNA[J].Science,2009,323(5917):1057-1060.
9 Fernandes-Alnemri T,Yu JW,Datta P,et al.AIM2 activates the inflammasome and cell death in response to cytoplasmic DNA[J].Nature,2009,458(7237):509-513.
10 Hakimi M,Peters A,Becker A,et al.Inflammation-related induction of absent in melanoma 2(AIM2)in vascular cells and atherosclerotic lesions suggests a role in vascular pathogenesis[J].J Vasc Surg,2014,59(3):794-803.
11 Kopfnagel V,Wittmann M,Werfel T.Human keratinocytes express AIM2 and respond to dsDNA with IL-1β secretion[J].Exp Dermatol,2011,20(12):1027-1029.
12 Dombrowski Y,Peric M,Koglin S,et al.Cytosolic DNA triggers inflammasome activation in keratinocytes in psoriatic lesions[J].Sci Transl Med,2011,3(82):82-91.
13 Akira S,Uematsu S,Takeuchi O.Pathogen recognition and innate immunity[J].Cell,2006,124(4):783-801.
14 Choubey D,Walter S,Geng Y,et al.Cytoplasmic localization of the interferon-inducible protein that is encoded by the AIM2(absent in melanoma)gene from the 200-gene family[J].FEBS Lett,2000,474(1):38-42.
15 Wang LJ,Hsu CW,Chen CC,et al.Interactome-wide analysis identifies end-binding protein 1 as a crucial component for the speck-like particle formation of activated absence in melanoma 2(AIM2)inflammasomes[J].Mol Cell Proteomics,2012,11(11):1230-1244.
16 Chen LC,Wang LJ,Tsang NM,et al.Tumour inflammasome-derived IL-1β recruits neutrophils and improves local recurrence-free survival in EBV-induced nasopharyngeal carcinoma[J].EMBO Mol Med,2012,4(12):1276-1293.
17 Kondo Y,Nagai K,Nakahata S,et al.Overexpression of the DNA sensor proteins,absent in melanoma 2 and interferon-inducible 16,contributes to tumorigenesis of oral squamous cell carcinoma with p53 inactivation[J].Cancer Sci,2012,103(4):782-790.
18 Kong H,Wang Y,Zeng X,et al.Differential expression of inflammasomes in lung cancer cell lines and tissues[J].Tumor Biol,2015,36(10):7501-7513.
19 Narayan G,Bourdon V,Chaganti S,et al.Gene dosage alterations revealed by cDNA microarray analysis in cervical cancer:identification of candidate amplified and overexpressed genes[J].Gene Chromosome Canc,2007,46(4):373-384.
20 Khosravi S,Wong RP,Ardekani GS,et al.Role of EIF5A2,a downstream target of Akt,in promoting melanoma cell invasion[J].Br J Cancer,2014,110(2):399-408.
21 Gaperov NM,Farkas SA,Nilsson TK,et al.Epigenetic activation of immune genes in cervical cancer[J].Immunol Lett,2014,162(2):256-257.
22 Torre LA,Bray F,Siegel RL,et al.Global cancer statistics,2012[J].CA Cancer J Clin,2015,65(2):87-108.
23 龙向淑,吴强,宋方,等.RAS信号途径参与干扰素-α抑制大鼠血管平滑肌细胞增殖[J].基础医学与临床,2014,34(7):882-885.
24 Lee J,Li L,Gretz N,et al.Absent in Melanoma 2(AIM2)is an important mediator of interferon-dependent and-independent HLA-DRA and HLA-DRB gene expression in colorectal cancers[J].Oncogene,2012,31(10):1242-1253.
25 Wang C,Wang X,Su Z,et al.The novel mTOR inhibitor Torin-2 induces autophagy and downregulates the expression of UHRF1 to suppress hepatocarcinoma cell growth[J].Oncol Rep,2015,34(4):1708-1716.
26 宋启斌,褚玉新,胡伟国.X线照射对THP1细胞中AIM2炎症小体的影响[J].现代免疫学,2014,34(6):466-470.

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