(3.237.234.213) 您好!臺灣時間:2021/03/09 12:51
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果

詳目顯示:::

我願授權國圖
: 
twitterline
研究生:莊育銘
研究生(外文):CHUANG, YU-MING
論文名稱:非典型STAT3調控SMARCAL1的表觀遺傳機制在胃癌癌變及免疫治療中的作用
論文名稱(外文):Epigenetic machinery of the transcriptional regulation of SMARCAL1 by non-canonical STAT3 in gastric tumorigenesis and immunotherapy
指導教授:陳永恩陳永恩引用關係
指導教授(外文):CHAN, WING-YAN
口試委員:吳淑芬劉宗霖林明宏
口試委員(外文):WU, SHU-FENLIU, TSUNGLINLIN, MING-HONG
口試日期:2020-07-29
學位類別:碩士
校院名稱:國立中正大學
系所名稱:生命科學系生物醫學研究所
學門:生命科學學門
學類:生物化學學類
論文種類:學術論文
論文出版年:2020
畢業學年度:108
語文別:英文
論文頁數:138
中文關鍵詞:胃癌表觀遺傳學
外文關鍵詞:Gastric CancerEpigeneticsSMARCAL1
相關次數:
  • 被引用被引用:0
  • 點閱點閱:32
  • 評分評分:系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔
  • 下載下載:0
  • 收藏至我的研究室書目清單書目收藏:0
  胃癌是全球常見的惡性腫瘤之一。STAT3激活參與在癌症惡化中,但其在表觀遺傳控制的角色仍不清楚。透過甲基組分析,我們比較不同STAT3活化差異的胃癌細胞AGS和胃癌病人樣本。透過電腦分析將顯著差異的甲基位點依據組蛋白修飾區域洗牌,並發現其在增強子標幟H3K4me1和抑制性標幟H3K27me3富集。因此STAT3相關甲基變化可能與增強子調控相關。有趣的是,在STAT3靶向的基因中,我們發現在SMARCAL1的拓樸關聯域中含有YY1的結合位,並在STAT3滅活後呈現低甲基化。出乎意料的是,差異甲基化區域並不是發生在CpG島,而是發生在CpG島岸。通過表達量與甲基化分析,我們發現SMARCAL1的表達量在腸化生中下調,並在腫瘤中上調。此外拓樸關聯域的甲基化會在染色體不穩定亞型的胃癌中劇烈變化。另外,我們也發現能穩定STAT3和DNMT1結合的STAT3乙酰化模擬物,能藉由增加甲基化和降低YY1在拓樸關聯域的占用來抑制SMARCAL1表達。由於SMARCAL1作用在複製叉逆轉,我們發現靶向SMARCAL1能增加對於DNA損傷的化療敏感度以及誘導cGAS/STING/一型IFN信號路徑,並增強癌症免疫治療的效果。
  Gastric cancer is one of the malignancies worldwide. Activation of STAT3 involved in cancer progression, but the role of STAT3 in epigenetic regulation remains unclear. By methylomic analysis, we compared AGS gastric cancer cells, cells depleted with STAT3 and gastric cancer patients with different STAT3 activation status. From computational analysis by shuffling CpGs with significant changes showed the differential methylated CpG sites were enriched with the enhancer and repressive histone marks, H3K4me1 and H3K27me3, respectively. It is suggested that STAT3 related methylation changes may relate to enhancer regulation. Interestingly, among the predicted STAT3 targets, we found that the center of topologically associating domain (TAD) containing YY1 binding in SMARCAL1, was hypomethylated under STAT3 depletion or inactivation. Unexpectedly, the differentially methylated region (DMR) was located at CpG island shore, but not at the CpG island. By expression and methylation analyses in gastric cancer progression, we found that SMARCAL1 was decreased in IM, but increased in gastric tumor. Additionally, the methylation status of TAD showed dramatic changes in CIN subtype. Furthermore, we also found that acetyl-mimic of STAT3, which is DNMT1 interaction form of STAT3, can suppress SMARCAL1 expression by increased DNA methylation and reduced YY1 occupancy at the TAD. As SMARCAL1 acts in replication fork reversal, we found that targeted SMARCAL1 would improve chemotherapy and induce cGAS/STING/Type I IFN pathway, for improving the efficiency of immunotherapy.
ACKNOWLEDGEMENTS I
摘要 II
ABSTRACT III
CHAPTER I INTRODUCTION 1
1.1 GENERAL INTRODUCTION 2
1.2 GASTRIC CANCER 4
1.2.1 Overview of Gastric Cancer 4
1.2.2 Epidemiology of Gastric Cancer 6
1.2.3 Etiology of Gastric Cancer 9
1.2.4 Pathogenesis of Gastric Cancer 11
1.2.5 Treatment for Gastric Cancer 13
1.3 CANCER GENOMIC ABERRATIONS OF GASTRIC CANCER 17
1.3.1 Genomic signature and subtypes of gastric cancer 17
1.3.2 Epstein-Barr virus (EBV) 19
1.3.3 Microsatellite instability (MSI) 19
1.3.4 Genomic stability (GS) 20
1.3.5 Chromosome instability (CIN) 20
1.4 EPIGENETIC MACHINERY 21
1.4.1 DNA methylation 21
1.4.2 Histone modification and Chromatin reprograming 22
1.4.3 Crosstalk between DNA methylation and Histone modification 23
1.5 JAK/STAT3 SIGNALING PATHWAY 25
1.5.1 Components and mechanisms of JAK/STAT3 pathway 25
1.5.2 The role of STAT3 in epigenetic regulation 27
1.5.3 Overview of JAK/STAT3 pathway in GC 27
1.6 SMARCAL1 28
1.6.1 Overview of SMARCAL1 28
1.6.2 Function of SMARCAL1 28
1.6.3 SMARCAL1 and cancer 29
1.7 DNA DAMAGE RESPONSES 30
1.7.1 DNA damage and cancer 30
1.7.2 DNA damage and immunotherapy 30
1.7.3 cGAS-STING pathway 31
1.8 OBJECTIVES OF STUDY 32
CHAPTER II MATERIALS AND METHODS 33
2.1 BIOINFORMATIC ANALYSIS 34
2.1.1 MBDcap sequencing analysis 34
2.1.2 Circos 36
2.1.3 MethylationEPIC BeadChip analysis 37
2.1.4 Shuffling CpG with histone modifications 38
2.1.5 Prediction of STAT3 binding sites 39
2.1.6 TF binding prediction around STAT3 39
2.1.7 UCSC xena 40
2.1.8 T cell responses signature 41
2.1.9 CIBERSORT 42
2.1.10 Statistics 43
2.2 BIOLOGICAL EXPERIMENTS 44
2.2.1 Site-directed mutagenesis 44
2.2.2 Cell culture 45
2.2.3 Transfection 45
2.2.4 Lentivirus production & Infection 46
2.2.5 Colony formation assay 47
2.2.6 Cell viability assay 47
2.2.7 Genomic DNA extraction 48
2.2.8 DNA dot blot 48
2.2.9 Bisulfite conversion 49
2.2.10 Bisulfite pyrosequencing 50
2.2.11 RNA extraction 51
2.2.12 Quantitative Reverse Transcription-PCR 52
2.2.13 Protein extraction 53
2.2.14 Western Blot 53
2.2.15 ChIP-qPCR analysis 54
CHAPTER III RESULTS 57
3.1 STAT3-MEDAITED HYPERMETHYLATION WAS OVERREPRESENTED IN PROMOTER REGIONS AND H3K27ME3 58
3.1.1 STAT3-mediated hypermethylation in promoter regions 58
3.1.2 Hypermethylation loci co-localized with STAT3 binding sites 61
3.1.3 Hypermethylation loci were overrepresented with H3K27me3 64
3.2 IDENTIFICATION OF SMARCAL1 WITH HYPERMETHYLATION. 67
3.2.1 Identified SMARCAL1 with STAT3 binding from STAT3-related hypermethylated loci. 67
3.3 STAT3-DNMT1 COMPLEX REPRESSED SMARCAL1 EXPRESSION AND REDUCED YY1 OCCUPANCY 72
3.3.1 Construction of gastric cancer cell s with STAT3-DNMT1 constitutive interaction mutation 72
3.3.2 STAT3-DNMT complex maintained global methyl cytosine and reduced global hydroxymethyl cytosine 75
3.3.3 STAT3 specific binding repressed SMARCAL1 expression and increased methylation 77
3.3.4 Hypermethylation only presented on CpG island shore, rather than CpG island 79
3.3.5 The increased methylation on CpG island shore reduced YY1 occupancy 82
3.4 THE CLINICAL SIGNIFICANCES ABOUT METHYLATION AND EXPRESSION OF SAMRCAL1 84
3.4.1 Hypomethylation of SMARCAL1 were frequently observed in CIN subtype of gastric cancer 84
3.4.2 SMARCAL1 was upregulated in cancer, but downregulated in intestinal metaplasia 86
3.4.3 Inverse correlation between SMARCAL1 expression and methylation 88
3.4.4 Hypomethylation of SMARCAL1 in intestinal type gastric cancer 92
3.5 TARGETING SMARCAL1 COULD AS A THERAPEUTIC STRATEGY FOR GASTRIC CANCER 94
3.5.1 SMARCAL1 knockdown enhanced the sensitivity to DNA damage agents 94
3.5.2 SMARCAL1 knockdown increased cGAS level and IFNB1 expression 97
3.5.3 CIN subtype gastric cancer was related with low T cell response signature 99
3.5.4 Endogenous replication stress were highly related with macrophage proportion in gastric cancer 102
CHAPTER IV CONCLUSION & DISCUSSION 104
4.1 CONCLUSION 105
4.2 THE REGULATION OF SMARCAL1 IN PRE-CANCEROUS LESION 107
4.3 THE IMPLICATION OF ENDOGENOUS REPLICATION STRESS IN CANCER 109
4.4 LIMITATION OF THIS STUDY 110
CHAPTER V TABLES 112
CHAPTER VI REFERENCES 118

1.Peleteiro, B., et al., Prevalence of Helicobacter pylori infection worldwide: a systematic review of studies with national coverage. Dig Dis Sci, 2014. 59(8): p. 1698-709.
2.Tan, P. and K.G. Yeoh, Genetics and Molecular Pathogenesis of Gastric Adenocarcinoma. Gastroenterology, 2015. 149(5): p. 1153-1162 e3.
3.Comprehensive molecular characterization of gastric adenocarcinoma. Nature, 2014. 513(7517): p. 202-9.
4.Fichtner-Feigl, S., R. Kesselring, and W. Strober, Chronic inflammation and the development of malignancy in the GI tract. Trends Immunol, 2015. 36(8): p. 451-9.
5.Kim, D.Y., et al., STAT3 expression in gastric cancer indicates a poor prognosis. J Gastroenterol Hepatol, 2009. 24(4): p. 646-51.
6.Nakashima, K., et al., Synergistic signaling in fetal brain by STAT3-Smad1 complex bridged by p300. Science, 1999. 284(5413): p. 479-82.
7.Wu, C.S., et al., Aberrant JAK/STAT Signaling Suppresses TFF1 and TFF2 through Epigenetic Silencing of GATA6 in Gastric Cancer. Int J Mol Sci, 2016. 17(9).
8.Yeh, C.M., et al., Epigenetic silencing of the NR4A3 tumor suppressor, by aberrant JAK/STAT signaling, predicts prognosis in gastric cancer. Sci Rep, 2016. 6: p. 31690.
9.Lee, H., et al., Acetylated STAT3 is crucial for methylation of tumor-suppressor gene promoters and inhibition by resveratrol results in demethylation. Proc Natl Acad Sci U S A, 2012. 109(20): p. 7765-9.
10.Weichert, W., et al., Association of patterns of class I histone deacetylase expression with patient prognosis in gastric cancer: a retrospective analysis. Lancet Oncol, 2008. 9(2): p. 139-48.
11.Cox, K.E., A. Marechal, and R.L. Flynn, SMARCAL1 Resolves Replication Stress at ALT Telomeres. Cell Rep, 2016. 14(5): p. 1032-1040.
12.Kolinjivadi, A.M., et al., Smarcal1-Mediated Fork Reversal Triggers Mre11-Dependent Degradation of Nascent DNA in the Absence of Brca2 and Stable Rad51 Nucleofilaments. Mol Cell, 2017. 67(5): p. 867-881 e7.
13.Puccetti, M.V., et al., Smarcal1 and Zranb3 Protect Replication Forks from Myc-Induced DNA Replication Stress. Cancer Res, 2019. 79(7): p. 1612-1623.
14.Bray, F., et al., Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2018. 68(6): p. 394-424.
15.Berlth, F., et al., Pathohistological classification systems in gastric cancer: diagnostic relevance and prognostic value. World J Gastroenterol, 2014. 20(19): p. 5679-84.
16.Waldum, H.L. and R. Fossmark, Types of Gastric Carcinomas. Int J Mol Sci, 2018. 19(12).
17.Ferlay, J., et al., Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods. Int J Cancer, 2019. 144(8): p. 1941-1953.
18.Chang, J.S., et al., The Epidemiology of Gastric Cancers in the Era of Helicobacter pylori Eradication: A Nationwide Cancer Registry-Based Study in Taiwan. Cancer Epidemiol Biomarkers Prev, 2019. 28(10): p. 1694-1703.
19.Katona, B.W. and A.K. Rustgi, Gastric Cancer Genomics: Advances and Future Directions. Cell Mol Gastroenterol Hepatol, 2017. 3(2): p. 211-217.
20.Chou, N.H., et al., Isocitrate Dehydrogenase 2 Dysfunction Contributes to 5-hydroxymethylcytosine Depletion in Gastric Cancer Cells. Anticancer Res, 2016. 36(8): p. 3983-90.
21.Maeda, M., et al., High impact of methylation accumulation on metachronous gastric cancer: 5-year follow-up of a multicentre prospective cohort study. Gut, 2017. 66(9): p. 1721-1723.
22.Hooi, J.K.Y., et al., Global Prevalence of Helicobacter pylori Infection: Systematic Review and Meta-Analysis. Gastroenterology, 2017. 153(2): p. 420-429.
23.Ding, S.Z., J.B. Goldberg, and M. Hatakeyama, Helicobacter pylori infection, oncogenic pathways and epigenetic mechanisms in gastric carcinogenesis. Future Oncol, 2010. 6(5): p. 851-62.
24.Bridge, D.R., et al., Creation and Initial Characterization of Isogenic Helicobacter pylori CagA EPIYA Variants Reveals Differential Activation of Host Cell Signaling Pathways. Sci Rep, 2017. 7(1): p. 11057.
25.Bustamante-Rengifo, J.A., et al., Effect of treatment failure on the CagA EPIYA motif in Helicobacter pylori strains from Colombian subjects. World J Gastroenterol, 2017. 23(11): p. 1980-1989.
26.Tredaniel, J., et al., Tobacco smoking and gastric cancer: review and meta-analysis. Int J Cancer, 1997. 72(4): p. 565-73.
27.Lauby-Secretan, B., et al., Body Fatness and Cancer--Viewpoint of the IARC Working Group. N Engl J Med, 2016. 375(8): p. 794-8.
28.Murphy, G., et al., Meta-analysis shows that prevalence of Epstein-Barr virus-positive gastric cancer differs based on sex and anatomic location. Gastroenterology, 2009. 137(3): p. 824-33.
29.Hino, R., et al., Activation of DNA methyltransferase 1 by EBV latent membrane protein 2A leads to promoter hypermethylation of PTEN gene in gastric carcinoma. Cancer Res, 2009. 69(7): p. 2766-74.
30.Fang, X., et al., Landscape of dietary factors associated with risk of gastric cancer: A systematic review and dose-response meta-analysis of prospective cohort studies. Eur J Cancer, 2015. 51(18): p. 2820-32.
31.Huang, K.K., et al., Genomic and Epigenomic Profiling of High-Risk Intestinal Metaplasia Reveals Molecular Determinants of Progression to Gastric Cancer. Cancer Cell, 2018. 33(1): p. 137-150 e5.
32.Eaton, K.A., et al., Helicobacter pylori with a truncated lipopolysaccharide O chain fails to induce gastritis in SCID mice injected with splenocytes from wild-type C57BL/6J mice. Infect Immun, 2004. 72(7): p. 3925-31.
33.Smyth, E.C., et al., Gastric cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol, 2016. 27(suppl 5): p. v38-v49.
34.Cunningham, D., et al., Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med, 2006. 355(1): p. 11-20.
35.Trip, A.K., et al., IMRT limits nephrotoxicity after chemoradiotherapy for gastric cancer. Radiother Oncol, 2014. 112(2): p. 289-94.
36.Yuan, D.D., et al., Targeted therapy for gastric cancer: Current status and future directions (Review). Oncol Rep, 2016. 35(3): p. 1245-54.
37.Lordick, F., K. Shitara, and Y.Y. Janjigian, New agents on the horizon in gastric cancer. Ann Oncol, 2017. 28(8): p. 1767-1775.
38.Kelly, R.J., Immunotherapy for Esophageal and Gastric Cancer. Am Soc Clin Oncol Educ Book, 2017. 37: p. 292-300.
39.Kang, Y.K., et al., Nivolumab in patients with advanced gastric or gastro-oesophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet, 2017. 390(10111): p. 2461-2471.
40.Jansen, C.S., et al., An intra-tumoral niche maintains and differentiates stem-like CD8 T cells. Nature, 2019.
41.Chia, N.Y. and P. Tan, Molecular classification of gastric cancer. Ann Oncol, 2016. 27(5): p. 763-9.
42.Wang, K., et al., Whole-genome sequencing and comprehensive molecular profiling identify new driver mutations in gastric cancer. Nat Genet, 2014. 46(6): p. 573-82.
43.Sohn, B.H., et al., Clinical Significance of Four Molecular Subtypes of Gastric Cancer Identified by The Cancer Genome Atlas Project. Clin Cancer Res, 2017.
44.Shibata, D. and L.M. Weiss, Epstein-Barr virus-associated gastric adenocarcinoma. Am J Pathol, 1992. 140(4): p. 769-74.
45.Takada, K., Epstein-Barr virus and gastric carcinoma. Mol Pathol, 2000. 53(5): p. 255-61.
46.Cristescu, R., et al., Molecular analysis of gastric cancer identifies subtypes associated with distinct clinical outcomes. Nat Med, 2015. 21(5): p. 449-56.
47.Yu, H. and R. Jove, The STATs of cancer--new molecular targets come of age. Nat Rev Cancer, 2004. 4(2): p. 97-105.
48.Weber, M., et al., Distribution, silencing potential and evolutionary impact of promoter DNA methylation in the human genome. Nat Genet, 2007. 39(4): p. 457-66.
49.Cavalli, G. and E. Heard, Advances in epigenetics link genetics to the environment and disease. Nature, 2019. 571(7766): p. 489-499.
50.Wu, X. and Y. Zhang, TET-mediated active DNA demethylation: mechanism, function and beyond. Nat Rev Genet, 2017. 18(9): p. 517-534.
51.Li, Y., et al., Stella safeguards the oocyte methylome by preventing de novo methylation mediated by DNMT1. Nature, 2018. 564(7734): p. 136-140.
52.Das, P.M. and R. Singal, DNA methylation and cancer. J Clin Oncol, 2004. 22(22): p. 4632-42.
53.Koch, A., et al., Analysis of DNA methylation in cancer: location revisited. Nat Rev Clin Oncol, 2018. 15(7): p. 459-466.
54.Issa, J.P., CpG island methylator phenotype in cancer. Nat Rev Cancer, 2004. 4(12): p. 988-93.
55.Issa, J.P., Methylation and prognosis: of molecular clocks and hypermethylator phenotypes. Clin Cancer Res, 2003. 9(8): p. 2879-81.
56.Jones, P.A., J.P. Issa, and S. Baylin, Targeting the cancer epigenome for therapy. Nat Rev Genet, 2016. 17(10): p. 630-41.
57.Jenuwein, T. and C.D. Allis, Translating the histone code. Science, 2001. 293(5532): p. 1074-80.
58.Bannister, A.J. and T. Kouzarides, Regulation of chromatin by histone modifications. Cell Res, 2011. 21(3): p. 381-95.
59.Lawrence, M., S. Daujat, and R. Schneider, Lateral Thinking: How Histone Modifications Regulate Gene Expression. Trends Genet, 2016. 32(1): p. 42-56.
60.Tessarz, P. and T. Kouzarides, Histone core modifications regulating nucleosome structure and dynamics. Nat Rev Mol Cell Biol, 2014. 15(11): p. 703-8.
61.Audia, J.E. and R.M. Campbell, Histone Modifications and Cancer. Cold Spring Harb Perspect Biol, 2016. 8(4): p. a019521.
62.Michalak, E.M., et al., The roles of DNA, RNA and histone methylation in ageing and cancer. Nat Rev Mol Cell Biol, 2019. 20(10): p. 573-589.
63.Sabari, B.R., et al., Metabolic regulation of gene expression through histone acylations. Nat Rev Mol Cell Biol, 2017. 18(2): p. 90-101.
64.Bennett, R.L. and J.D. Licht, Targeting Epigenetics in Cancer. Annu Rev Pharmacol Toxicol, 2018. 58: p. 187-207.
65.Fujisawa, T. and P. Filippakopoulos, Functions of bromodomain-containing proteins and their roles in homeostasis and cancer. Nat Rev Mol Cell Biol, 2017. 18(4): p. 246-262.
66.D'Urso, A. and J.H. Brickner, Mechanisms of epigenetic memory. Trends Genet, 2014. 30(6): p. 230-6.
67.Monk, D., Germline-derived DNA methylation and early embryo epigenetic reprogramming: The selected survival of imprints. Int J Biochem Cell Biol, 2015. 67: p. 128-38.
68.Cedar, H. and Y. Bergman, Linking DNA methylation and histone modification: patterns and paradigms. Nat Rev Genet, 2009. 10(5): p. 295-304.
69.Du, J., et al., DNA methylation pathways and their crosstalk with histone methylation. Nat Rev Mol Cell Biol, 2015. 16(9): p. 519-32.
70.Charlet, J., et al., Bivalent Regions of Cytosine Methylation and H3K27 Acetylation Suggest an Active Role for DNA Methylation at Enhancers. Mol Cell, 2016. 62(3): p. 422-431.
71.Vire, E., et al., The Polycomb group protein EZH2 directly controls DNA methylation. Nature, 2006. 439(7078): p. 871-4.
72.Wegenka, U.M., et al., Acute-phase response factor, a nuclear factor binding to acute-phase response elements, is rapidly activated by interleukin-6 at the posttranslational level. Mol Cell Biol, 1993. 13(1): p. 276-88.
73.Lutticken, C., et al., Association of transcription factor APRF and protein kinase Jak1 with the interleukin-6 signal transducer gp130. Science, 1994. 263(5143): p. 89-92.
74.Zhong, Z., Z. Wen, and J.E. Darnell, Jr., Stat3: a STAT family member activated by tyrosine phosphorylation in response to epidermal growth factor and interleukin-6. Science, 1994. 264(5155): p. 95-8.
75.Ward, L.D., et al., Influence of interleukin-6 (IL-6) dimerization on formation of the high affinity hexameric IL-6.receptor complex. J Biol Chem, 1996. 271(33): p. 20138-44.
76.Lupardus, P.J., et al., Structural snapshots of full-length Jak1, a transmembrane gp130/IL-6/IL-6Ralpha cytokine receptor complex, and the receptor-Jak1 holocomplex. Structure, 2011. 19(1): p. 45-55.
77.Wen, Z., Z. Zhong, and J.E. Darnell, Jr., Maximal activation of transcription by Stat1 and Stat3 requires both tyrosine and serine phosphorylation. Cell, 1995. 82(2): p. 241-50.
78.Decker, T. and P. Kovarik, Serine phosphorylation of STATs. Oncogene, 2000. 19(21): p. 2628-37.
79.Harhous, Z., et al., An Update on the Multifaceted Roles of STAT3 in the Heart. Front Cardiovasc Med, 2019. 6: p. 150.
80.Pan, Y.M., et al., STAT3 signaling drives EZH2 transcriptional activation and mediates poor prognosis in gastric cancer. Mol Cancer, 2016. 15(1): p. 79.
81.Zhang, Q., et al., STAT3 induces transcription of the DNA methyltransferase 1 gene (DNMT1) in malignant T lymphocytes. Blood, 2006. 108(3): p. 1058-64.
82.Ellmark, P., et al., Identification of protein expression signatures associated with Helicobacter pylori infection and gastric adenocarcinoma using recombinant antibody microarrays. Mol Cell Proteomics, 2006. 5(9): p. 1638-46.
83.Jackson, C.B., et al., Augmented gp130-mediated cytokine signalling accompanies human gastric cancer progression. J Pathol, 2007. 213(2): p. 140-51.
84.Sugimoto, M., et al., Helicobacter pylori outer membrane proteins on gastric mucosal interleukin 6 and 11 expression in Mongolian gerbils. J Gastroenterol Hepatol, 2011. 26(11): p. 1677-84.
85.Bronte-Tinkew, D.M., et al., Helicobacter pylori cytotoxin-associated gene A activates the signal transducer and activator of transcription 3 pathway in vitro and in vivo. Cancer Res, 2009. 69(2): p. 632-9.
86.Yu, S., et al., The prognostic value of pSTAT3 in gastric cancer: a meta-analysis. J Cancer Res Clin Oncol, 2016. 142(3): p. 649-57.
87.Coleman, M.A., J.A. Eisen, and H.W. Mohrenweiser, Cloning and characterization of HARP/SMARCAL1: a prokaryotic HepA-related SNF2 helicase protein from human and mouse. Genomics, 2000. 65(3): p. 274-82.
88.Muthuswami, R., et al., A eukaryotic SWI2/SNF2 domain, an exquisite detector of double-stranded to single-stranded DNA transition elements. J Biol Chem, 2000. 275(11): p. 7648-55.
89.Yusufzai, T. and J.T. Kadonaga, HARP is an ATP-driven annealing helicase. Science, 2008. 322(5902): p. 748-50.
90.Boerkoel, C.F., et al., Mutant chromatin remodeling protein SMARCAL1 causes Schimke immuno-osseous dysplasia. Nat Genet, 2002. 30(2): p. 215-20.
91.Yusufzai, T., et al., The annealing helicase HARP is recruited to DNA repair sites via an interaction with RPA. Genes Dev, 2009. 23(20): p. 2400-4.
92.Lugli, N., S.K. Sotiriou, and T.D. Halazonetis, The role of SMARCAL1 in replication fork stability and telomere maintenance. DNA Repair (Amst), 2017. 56: p. 129-134.
93.Heaphy, C.M., et al., Prevalence of the alternative lengthening of telomeres telomere maintenance mechanism in human cancer subtypes. Am J Pathol, 2011. 179(4): p. 1608-15.
94.Bartkova, J., et al., Oncogene-induced senescence is part of the tumorigenesis barrier imposed by DNA damage checkpoints. Nature, 2006. 444(7119): p. 633-7.
95.Halazonetis, T.D., V.G. Gorgoulis, and J. Bartek, An oncogene-induced DNA damage model for cancer development. Science, 2008. 319(5868): p. 1352-5.
96.Lord, C.J. and A. Ashworth, The DNA damage response and cancer therapy. Nature, 2012. 481(7381): p. 287-94.
97.Kim, J., et al., Tumor Mutational Burden Determined by Panel Sequencing Predicts Survival After Immunotherapy in Patients With Advanced Gastric Cancer. Front Oncol, 2020. 10: p. 314.
98.Mouw, K.W., et al., DNA Damage and Repair Biomarkers of Immunotherapy Response. Cancer Discov, 2017. 7(7): p. 675-693.
99.Rospo, G., et al., Evolving neoantigen profiles in colorectal cancers with DNA repair defects. Genome Med, 2019. 11(1): p. 42.
100.Li, T. and Z.J. Chen, The cGAS-cGAMP-STING pathway connects DNA damage to inflammation, senescence, and cancer. J Exp Med, 2018. 215(5): p. 1287-1299.
101.Sen, T., et al., Targeting DNA Damage Response Promotes Antitumor Immunity through STING-Mediated T-cell Activation in Small Cell Lung Cancer. Cancer Discov, 2019. 9(5): p. 646-661.
102.Wu, J., et al., Cyclic GMP-AMP is an endogenous second messenger in innate immune signaling by cytosolic DNA. Science, 2013. 339(6121): p. 826-30.
103.Ishikawa, H., Z. Ma, and G.N. Barber, STING regulates intracellular DNA-mediated, type I interferon-dependent innate immunity. Nature, 2009. 461(7265): p. 788-92.
104.Zhang, C., et al., Structural basis of STING binding with and phosphorylation by TBK1. Nature, 2019. 567(7748): p. 394-398.
105.Motwani, M., S. Pesiridis, and K.A. Fitzgerald, DNA sensing by the cGAS-STING pathway in health and disease. Nat Rev Genet, 2019. 20(11): p. 657-674.
106.Schadt, L., et al., Cancer-Cell-Intrinsic cGAS Expression Mediates Tumor Immunogenicity. Cell Rep, 2019. 29(5): p. 1236-1248 e7.
107.Li, W., et al., cGAS-STING-mediated DNA sensing maintains CD8(+) T cell stemness and promotes antitumor T cell therapy. Sci Transl Med, 2020. 12(549).
108.Chen, Q., et al., Carcinoma-astrocyte gap junctions promote brain metastasis by cGAMP transfer. Nature, 2016. 533(7604): p. 493-498.
109.Wu, J., et al., Interferon-Independent Activities of Mammalian STING Mediate Antiviral Response and Tumor Immune Evasion. Immunity, 2020. 53(1): p. 115-126 e5.
110.Marloye, M., S.E. Lawler, and G. Berger, Current patent and clinical status of stimulator of interferon genes (STING) agonists for cancer immunotherapy. Pharm Pat Anal, 2019. 8(4): p. 87-90.
111.Neary, J.L., et al., Comparative analysis of MBD-seq and MeDIP-seq and estimation of gene expression changes in a rodent model of schizophrenia. Genomics, 2017. 109(3-4): p. 204-213.
112.Kang, H.J., et al., Disruption of STAT3-DNMT1 interaction by SH-I-14 induces re-expression of tumor suppressor genes and inhibits growth of triple-negative breast tumor. Oncotarget, 2017. 8(48): p. 83457-83468.
113.Yuan, Z.L., et al., Stat3 dimerization regulated by reversible acetylation of a single lysine residue. Science, 2005. 307(5707): p. 269-73.
114.Jones, P.A. and S.B. Baylin, The fundamental role of epigenetic events in cancer. Nat Rev Genet, 2002. 3(6): p. 415-28.
115.Weintraub, A.S., et al., YY1 Is a Structural Regulator of Enhancer-Promoter Loops. Cell, 2017. 171(7): p. 1573-1588 e28.
116.Kim, J., et al., Methylation-sensitive binding of transcription factor YY1 to an insulator sequence within the paternally expressed imprinted gene, Peg3. Hum Mol Genet, 2003. 12(3): p. 233-45.
117.Poole, L.A., et al., SMARCAL1 maintains telomere integrity during DNA replication. Proc Natl Acad Sci U S A, 2015. 112(48): p. 14864-9.
118.Pantelidou, C., et al., PARP Inhibitor Efficacy Depends on CD8(+) T-cell Recruitment via Intratumoral STING Pathway Activation in BRCA-Deficient Models of Triple-Negative Breast Cancer. Cancer Discov, 2019. 9(6): p. 722-737.
119.Cheng, W.C., et al., Uncoupling protein 2 reprograms the tumor microenvironment to support the anti-tumor immune cycle. Nat Immunol, 2019. 20(2): p. 206-217.
120.Rodriquenz, M.G., et al., MSI and EBV Positive Gastric Cancer's Subgroups and Their Link With Novel Immunotherapy. J Clin Med, 2020. 9(5).
121.Chen, B., et al., Profiling Tumor Infiltrating Immune Cells with CIBERSORT. Methods Mol Biol, 2018. 1711: p. 243-259.
122.Yao, Y.L., W.M. Yang, and E. Seto, Regulation of transcription factor YY1 by acetylation and deacetylation. Mol Cell Biol, 2001. 21(17): p. 5979-91.
123.Pietrocola, F., et al., Acetyl coenzyme A: a central metabolite and second messenger. Cell Metab, 2015. 21(6): p. 805-21.
124.Wilkinson, F.H., K. Park, and M.L. Atchison, Polycomb recruitment to DNA in vivo by the YY1 REPO domain. Proc Natl Acad Sci U S A, 2006. 103(51): p. 19296-301.
125.Burnet, M., Cancer: a biological approach. III. Viruses associated with neoplastic conditions. IV. Practical applications. Br Med J, 1957. 1(5023): p. 841-7.
126.Jaiswal, S., et al., Macrophages as mediators of tumor immunosurveillance. Trends Immunol, 2010. 31(6): p. 212-9.


電子全文 電子全文(網際網路公開日期:20250810)
QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top
系統版面圖檔 系統版面圖檔