肠癌中雌激素受体β与核因子κB互作分析  

Analysis of interaction between estrogen receptorβand nuclear factor-κB in colorectal cancer

作　　者：彭延杰 张金佩 田家齐 陈震 梁梨杨 张林[1] 宋丹丹 PENG Yanjie;ZHANG Jinpei;TIAN Jiaqi;CHEN Zhen;LIANG Liyang;ZHANG Lin;SONG Dandan(Clinical Medical Research Center for Women and Children Diseases,Key Laboratory of Birth Defect Prevention and Genetic Medicine of Shandong Health Commission,Maternal and Child Health Care Hospital of Shandong Province,Jinan 250014,China;Key Laboratory of Evidence Science(China University of Political Science and Law),Ministry of Education,Beijing 100088,China;Department of Public Health,Weifang Medical University,Weifang 063053,China;Can-cer Surgery Department,Tangshan Workers'Hospital,Tangshan 063000,China)

机构地区：[1]青岛大学附属山东省妇幼保健院妇女儿童疾病临床医学研究中心,山东省医药卫生出生缺陷防治与遗传医学重点实验室,山东济南250014 [2]中国政法大学证据科学教育部重点实验室,北京100088 [3]潍坊医学院公共卫生学院,山东潍坊261053 [4]唐山市工人医院肿瘤外科,河北唐山063000

出　　处：《中国病理生理杂志》2024年第11期2041-2049,共9页Chinese Journal of Pathophysiology

基　　金：山东省自然科学基金青年项目(No.ZR2022QH339)。

摘　　要：目的:结直肠癌是全球第三大常见肿瘤,核因子κB(nuclear factor-κB,NF-κB)和激活蛋白1(acti-vator protein-1,AP-1)已被证实可促进结直肠癌的发生,而ERβ在肿瘤发生过程中具有保护作用。然而NF-κB和AP-1是否存在协同作用,且与ERβ是否存在蛋白互作尚不清楚。本文通过分析肿瘤坏死因子α(tumor necrosis fac-torα,TNF-α)处理后的结肠癌细胞系HT29和SW480探索ERβ、NF-κB和AP-1在结肠癌中的交互作用机制。方法:利用TNF-α转录组测序结果,综合p65和ERβ染色质免疫沉淀测序结果,利用R语言在肠癌细胞系HT29和SW480中构建TNF-α、NF-κB/p65和ERβ互作网络,探索蛋白互作关系。结果:TNF-α通过p65的DNA结合调控一部分基因的表达,这些基因主要富集在NF-κB和丝裂原激活蛋白激酶(mitogen-activated protein kinase,MAPK)通路。NF-κB/p65和MAPK通路的组分与AP-1家族蛋白存在潜在的相互作用。ERβ的过表达并未显著影响TNF-α介导的基因调控,但可能通过MAPK和磷脂酰肌醇3激酶(phosphatidylinositol 3-kinase,PI3K)/Akt途径调节AP-1的活性。此外,ERβ降低了HT29中p65的DNA结合位点,增加了SW480中的p65结合位点,提示ERβ对NF-κB的调控与细胞性别相关。结论:在结直肠癌中NF-κB、ERβ和AP-1存在潜在交互作用:TNF-α可通过NF-κB调控AP-1,而过表达ERβ可以改变NF-κB介导的调控作用,且ERβ对NF-κB的影响可能与性别有关。AIM:To investigate the interaction mechanisms of estrogen receptorβ(ERβ),nuclear factor-κB(NF-κB)and activator protein-1(AP-1)in colorectal cancer by analyzing the transcriptome data after tumor necrosis fac-torα(TNF-α)treatment and combining it with NF-κB/p65 and ERβcistrome data in colon cancer cell lines HT29 and SW480.METHODS:The TNF-αtranscriptome was integrated with p65 and ERβcistrome data.Protein interaction net-works of TNF-α,NF-κB/p65 and ERβwere constructed in colon cancer cell lines HT29 and SW480 using R.RE-SULTS:TNF-αregulated genes through p65 DNA binding,which were mainly enriched in the NF-κB and mitogen-acti-vated protein kinase(MAPK)pathways.Components of the NF-κB/p65 and MAPK pathways had potential interactions with AP-1 family proteins.ERβoverexpression did not significantly affect TNF-α-mediated gene regulation but may regu-late AP-1 activity through the MAPK and phosphatidylinositol 3-kinase(PI3K)/Akt pathways.Furthermore,ERβde-creased p65 DNA binding sites in HT29 but increased p65 binding sites in SW480,suggesting cell line-specific regulation of NF-κB by ERβ.CONCLUSION:In colorectal cancer,NF-κB,ERβand AP-1 have potential interactions:TNF-αcan regulate AP-1 through NF-κB,while ERβoverexpression can alter NF-κB-mediated regulation,and the influence of ERβon NF-κB may be gender-related.

关 键 词：肠道肿瘤 雌激素受体Β 核因子ΚB 蛋白质相互作用 

分 类 号：R735.3[医药卫生—肿瘤] R363[医药卫生—临床医学] R857.3