STAT1与STAT3在肝细胞癌及肝衰竭发病机制中的作用

高梦丹; 张永宏; 赵艳

doi:10.3969/j.issn.1001-5256.2018.09.040

STAT1与STAT3在肝细胞癌及肝衰竭发病机制中的作用

DOI: 10.3969/j.issn.1001-5256.2018.09.040

首都医科大学附属北京佑安医院临床检验中心

基金项目:

北京市医管局“扬帆计划”重点专业(ZYLX201711)；传染病相关疾病生物标志物北京市重点实验室(BZ0373)；丰台区科技项目(BJYAH2015YN15)；

详细信息

中图分类号: R735.7;R575.3
计量
- 文章访问数: 2326
- HTML全文浏览量: 52
- PDF下载量: 398
- 被引次数: 0
出版历程
- 收稿日期: 2018-06-01
- 出版日期: 2018-09-20

Role of signal transduction and transcription factors STAT1 and STAT3 in the pathogenesis of hepatocellular carcinoma and liver failure

Clinical Laboratory Center, Beijing You'An Hospital, Capital Medical University

Research funding:

摘要

摘要: 肝细胞癌(HCC)及肝衰竭为我国常见的肝脏疾病,其发病率及病死率极高,相关研究虽多但具体发病机制仍不详。通过介绍STAT1及STAT3磷酸化蛋白在HCC及肝衰竭发病机制中的多种作用,如:抗病毒防御、急性期反应、肝损伤、修复、炎症、转化等,了解其在HCC及肝衰竭发病机制中的具体作用,并以其为分子靶标研制相关药物,应用于临床,对于降低患者病死率具有重要意义。
- 癌,肝细胞 /
- 肝功能衰竭 /
- STAT1转录因子 /
- STAT3转录因子 /
- 综述
Abstract: Hepatocellular carcinoma (HCC) and liver failure are common liver diseases in China and have extremely high incidence and mortality rates. Although there are many related studies, the detailed pathogenesis of these two diseases is still unknown. This article reviews the role of STAT1 and STAT3 phosphorylation proteins in the pathogenesis of HCC and liver failure, such as antiviral defense, acute phase response, liver injury, repair, inflammation, and transformation. A deep understanding of their role in the pathogenesis of HCC and liver failure and the development of related drugs with them as molecular targets play an important role in reducing mortality rate in clinical practice.
- carcinoma, hepatocellular /
- liver failure /
- STAT1 transcription factor /
- STAT3 transcription factor /
- review

HTML全文

参考文献(36)

[1]RYERSON AB, EHEMAN CR, ALTEKRUSE SF, et al.Annual report to the nation on the status of cancer, 1975-2012, featuring the increasing incidence of liver cancer[J].Cancer, 2016, 122 (9) :1312-1337.

[2]YU JJ, YAN WT, QUAN B, et al.Recommendations for EASLClinical Practice Guidelines:Management of hepatocellular carcinoma (2018) [J].J Clin Hepatol, 2018, 34 (6) :1183-1186. (in Chinese) 余炯杰, 严文韬, 权冰, 等.《2018年欧洲肝病学会临床实践指南:肝细胞癌的管理》推荐意见[J].临床肝胆病杂志, 2018, 34 (6) :1183-1186.

[3] Liver Failure and Artificial Liver Group, Chinese Society of Infectious Diseases, CMA;Severe Liver Disease and Artificial Liver Group, Chinese Society of Hepatology, CMA.Guideline for diagnosis and treatment of liver failure[J].Chin J Clin Infect Dis, 2012, 5 (6) :321-327. (in Chinese) 中华医学会感染病学分会肝衰竭与人工肝学组, 中华医学会肝病学分会重型肝病与人工肝学组.肝衰竭诊治指南 (2012年版) [J].中华临床感染病杂志, 2012, 5 (6) :321-327.

[4] Chinese Society of Hepatology and Chinese Society of Infectious Diseases, Chinese Medical Association.The guideline of prevention and treatment for chronic hepatitis B (2010 version) [J].J Clin Hepatol, 2011, 27 (1) :I-XVI. (in Chinese) 中华医学会肝病学分会, 中华医学会感染病学分会.慢性乙型肝炎防治指南 (2010年版) [J].临床肝胆病杂志, 2011, 27 (1) :I-XVI.

[5]CAO XT.Medical immunology[M].6th edition, Beijing:People's Health Publishing House, 2015. (in Chinese) 曹雪涛.医学免疫学[M].第六版, 北京:人民卫生出版社, 2015.

[6]VARIKUTI S, OGHUMU S, ELBAZ M, et al.STAT1 gene deficient mice develop accelerated breast cancer growth and metastasis which is reduced by IL-17 blockade[J].Oncoimmunology, 2017, 6 (11) :e1361088.

[7]GAO B.Cytokines, STATs and liver disease[J].Cellular Mol Immunol, 2005, 2 (2) :92-100.

[8]NAJJAR I, FAGARD R.STAT1 and pathogens, not a friendly relationship[J].Biochimie, 2010, 92 (5) :425-444.

[9]KIM HS, LEE MS.STAT1 as a key modulator of cell death[J].Cell Signal, 2007, 19 (3) :454-465.

[10]WANG Y, YU X, SONG H, et al.The STAT-ROS cycle extends IFN-induced cancer cell apoptosis[J].Int J Oncol, 2018, 52 (1) :305-313.

[11]ZHANG Y, LIU Z.STAT1 in cancer:Friend or Foe?[J].Discov Med, 2017, 24 (130) :19-29.

[12]CHAN SR, VERMI W, LUO JQ, et al.STAT1-deficient mice spontaneously develop estrogen receptor a-positive luminal mammary carcinomas[J].Breast Cancer Res, 2012, 14:r16.

[13]LESINSKI GB, ANGHELINA M, ZIMMERER J, et al.The antitumor effects of IFN-αare abrogated in a STAT1-deficient mouse[J].J Clin Invest, 2003, 112 (2) :170-180.

[14]NAGAI H, NAKA T, TERADA Y, et al.Hypermethylation associated with inactivation of the SOCS-1 gene, a JAK/STAT inhibitor, in human hepatoblastomas[J].J Hum Genet, 2003, 48 (2) :65-69.

[15]CHIM CS, FUNG TK, CHEUNG WC, et al.SOCS1 and SHP1 hypermethylation in multiple myeloma:Implications for epigenetic activation of the Jak/STAT pathway[J].Blood, 2004, 103 (12) :4630-4635.

[16]COCHET O, FRELIN C, PEYRON JF, et al.Constitutive activation of STAT proteins in the HDLM-2 and L540 Hodgkin lymphoma-derived cell lines supports cell survival[J].Cell Signal, 2006, 18 (4) :449-455.

[17]GALM O, YOSHIKAWA H, ESTELLER M, et al.SOCS-1, a negative regulator of cytokine signaling, is frequently silenced by methylation in multiple myeloma[J].Blood, 2003, 101 (7) :2784-2788.

[18]TO KF, CHAN MW, LEUNG WK, et al.Constitutional activation of IL-6-mediated JAK/STAT pathway through hypermethylation of SOCS-1 in human gastric cancer cell line[J].Br J Cancer, 2004, 91 (7) :1335-1341.

[19]YOSHIKAWA H, MATSUBARA K, QIAN GS, et al.SOCS-1, a negative regulator of the JAK/STAT pathway, is silenced by methylation in human hepatocellular carcinoma and shows growth-suppression activity[J].Nat Genet, 2001, 28 (1) :29-35.

[20]CHUNG SS, WU Y, OKOBI Q, et al.Proinflammatory cytokines IL-6 and TNF-αincreased telomerase activity through NF-κB/STAT1/STAT3 activation, and withaferin a inhibited the signaling in colorectal cancer cells[J].Mediators Inflamm, 2017, 2017:5958429.

[21]AKRAM M, KIM KA, KIM ES, et al.Selective inhibition of JAK2/STAT1 signaling and i NOS expression mediates the anti-inflammatory effects of coniferyl aldehyde[J].Chem Biol Interact, 2016, 256:102-110.

[22]KAUR T, MUKHERJEA D, SHEEHAN K, et al.Short interfering RNA against STAT1 attenuates cisplatin-induced ototoxicity in the rat by suppressing inflammation[J].Cell Death Dis, 2011, 2:e180.

[23]SAMARDZIC T, JANKOVIC V, STOSIC-GRUJICIC S, et al.STAT1 is required for i NOS activation, but not IL-6 production in murine fibroblasts[J].Cytokine, 2001, 13 (3) :179-182.

[24]CAI JJ, GUO XL.Studies on telomerase reverse transcriptase components and liver cancer[J].Chin J Hepatol, 2016, 24 (7) :555-560. (in Chinese) 蔡嘉镜, 郭晓兰.端粒酶逆转录酶组分与肝癌研究[J].中华肝脏病杂志, 2016, 24 (7) :555-560.

[25]KO E, SEO HW, JUNG G.Telomere length and reactive oxygen species levels are positively associated with a high risk of mortality and recurrence in hepatocellular carcinoma[J].Hepatology, 2018, 67 (4) :1378-1391.

[26]YAN J, ZHOU Y, CHEN DX, et al.Effects of mitochondrial translocation of telomerase on drug resistance in hepatocellular carcinoma cells[J].J Cancer, 2015, 6 (2) :151-159.

[27]LI TF, SU CY, HUANG G, et al.IL-6 suppresses CCR7 expression in human monocyte-derived dendritic cells via STAT3 pathway[J].J Third Mil Med Univ, 2015, 37 (8) :751-756. (in Chinese) 李腾飞, 苏崇宇, 黄刚, 等, STAT3信号通路在IL-6抑制人单核细胞来源树突状细胞CCR7表达中的作用[J].第三军医大学学报, 2015, 37 (8) :751-756.

[28]XIONG QS, WU SS, WANG JW, et al.Hepatitis B virus promotes cancer cell migration by downregulating miR-340-5p expression to induce STAT3 overexpression[J].Cell Biosci, 2017, 7:16.

[29]WANG B, LIU T, WU JC, et al.STAT3 aggravates TGF-β1-induced hepatic epithelial-to-mesenchymal transition and migration[J].Biomed Pharmacother, 2018, 98:214-221.

[30]SHEN WX, CHEN CH, GUAN YY, et al.A pumpkin polysaccharide induces apoptosis by inhibiting the JAK2/STAT3 pathway in human hepatoma Hep G2 cells[J].Int J Biol Macromol, 2017, 104 (Pt A) :681-686.

[31]KIM HY, JHUN JY, CHO ML, et al.Interleukin-6 upregulates Th17 response via m TOR/STAT3 pathway in acute-on-chronic hepatitis B liver failure[J].J Gastroenterol, 2014, 49 (8) :1264-1273.

[32]KLEIN C, WVSTEFELD T, HEINRICH PC, et al.ME3738 protects from concanavalin A-induced liver failure via an IL-6-dependent mechanism[J].Eur J Immunol, 2003, 33 (8) :2251-2261.

[33]KIM SJ, CHO HI, KIM SJ, et al.Protective effect of linarin against D-galactosamine and lipopolysaccharide-induced fulminant hepatic failure[J].Eur J Pharmacol, 2014, 738 (10) :66-73.

[34]YANG NB, NI SL, LI SS, et al.Endotoxin tolerance alleviates experimental acute liver failure via inhibition of high mobility group box 1[J].Int J Clin Exp Pathol, 2015, 8 (8) :9062-9071.

[35]HO CH, FAN CK, YU HJ, et al.Testosterone suppresses uropathogenic Escherichia coli invasion and colonization within prostate cells and inhibits inflammatory responses through JAK/STAT-1 signaling pathway[J].PLo S One, 2017, 12 (6) :e0180244.

[36]WU XX, SUN Y, GUO WJ, et al.Rebuilding the balance of STAT1and STAT3 signalings by fusaruside, a cerebroside compound, for the treatment of T-cell-mediated fulminant hepatitis in mice[J].Biochem Pharmacol, 2012, 84 (9) :1164-1173.

施引文献

资源附件(0)

访问统计