摘要
目的 采用生物信息学分析肿瘤组织潜在侯选靶标及标志物ADAM17的结构和功能特点。方法 运用ProtParam和ProtScale、STRING12.0、The Human Protein Atlas和cBioPortal等不同数据库,对人ADAM17理化性质、跨膜区域、信号肽、核定位序列、磷酸化和糖基化位点、亚细胞定位、二级/三级结构、蛋白互作网络、不同肿瘤组织中的表达以及遗传改变等进行分析。采用免疫组化对肺、结肠组织的肿瘤组织和正常样本ADAM17表达进行验证。结果 人ADAM17是由824个氨基酸构成的亲水性蛋白;分子式为C_(4066)H_(6356)N_(1124)O_(1277)S_(50),理论等电点为5.50,平均亲水性为-0.573;定位于细胞质,具有1个跨膜结构域、1个信号肽以及2个核定位序列;二级结构主要由不规则卷曲组成,存在89个磷酸化位点、5个N-糖基化位点和9个O-糖基化位点;广泛分布于正常组织中,并在膀胱尿路上皮癌、宫颈鳞状细胞癌、结肠癌(COAD)、肾透明细胞癌、肝脏肝细胞癌和肺鳞状细胞癌(LUSC)中高表达,能与金属蛋白酶抑制因子3、表皮生长因子等主要蛋白发生相互作用,参与肿瘤坏死因子、核因子-κB等信号通路。免疫组化验证结果显示,ADAM17在人肺、结肠正常组织中低表达,而在LUSC、COAD组织中高表达。结论 ADAM17可能是肿瘤的潜在候选靶标及标志物。
Aim To analyze the structural and functional characteristics of potential candidate targets and biomarker ADAM17 in tumor tissue by using bioinformatics.Methods Different databases such as ProtParam,ProtScale,STRING 12.0,the Human Protein Atlas,and cBioPortal were used to analyze the physical and chemical properties,signal peptide,nuclear localization sequence,phosphorylation and glycosylation sites,subcellular localization,secondary/tertiary structure,protein-protein interaction network,expression differences in various tumor and genetic alteration.Immunohistochemistry was used to validate the expression of ADAM17 in tumor tissues and normal samples of lung and colon tissues.Results Human ADAM17 is a hydrophilic protein composed of 824 amino acids.The molecular formula is C_(4066)H_(6356)N_(1124)O_(1277)S_(50),the theoretical isoelectric point is 5.50,and the average hydrophilicity is-0.573.ADAM17 is localized in the cytoplasm with 1 transmembrane domain,1 signal peptide and 2 nuclear localization sequences.The secondary structure is mainly composed of irregular coils,with 89 possible phosphorylation sites,5 N-glycosylation sites and 9 O-glycosylation sites.ADAM17 is widely distributed in lots of normal tissues,and highly expressed in bladder urothelial carcinoma,cervical squamous cell carcinoma,colon cancer(COAD),kidney clear cell carcinoma,liver hepatocellular carcinoma and lung squamous cell carcinoma(LUSC),and can interact with major proteins such as metalloproteinase-3 and epidermal growth factor,involving in tumor necrosis factor,nuclear factor-κB signaling pathways.The immunohistochemical verification results show that,ADAM17 is lowly expressed in normal human lung and colon tissues,while is highly expressied in LUSC and COAD tissues.Conclusion ADAM17 may be a potential candidate target and biomarker for tumors.
作者
王道
徐洁欢
刘丹
陈建林
WANG Dao;XU Jiehuan;LIU Dan;CHEN Jianlin(Department of Obstetrics and Gynecology,the Second Xiangya Hospital,Central South University,Changsha 410011,Hunan,China;Changsha Health Vocational College,Changsha 410605,Hunan,China)
出处
《中南医学科学杂志》
CAS
2024年第5期705-710,共6页
Medical Science Journal of Central South China
基金
国家自然科学基金(82271674)
湖南省自然科学基金(2022JJ60110)
湖南省自然科学基金(2024JJ5469)。
