摘要
目的:生物信息学分析SPP1在肝细胞癌(HCC)中的表达及与临床预后的关系,并预测SPP1表达异常的分子机制。方法:GEPIA数据库分析SPP1 mRNA在肝细胞癌中的表达及与患者预后的关系;cBioPortal、MethHC、GCBI和StarBase和NetPhos 3.1 Server等数据库预测SPP1基因突变、启动子区甲基化水平、与SPP1结合的miRNAs转录后调控、蛋白翻译后修饰。结果:SPP1 mRNA在HCC中表达升高,其中SPP1高表达患者的总体预后差(log-rank P=0.00011)。HCC中SPP1存在基因扩增和深度缺失。启动子区甲基化水平降低(P<0.005),并与SPP1表达负相关(R=0.650,P<0.0001)。HCC中miR-146a表达降低,miR-146a能与SPP1的3’-UTR结合,miR-146a与SPP1的共表达有统计学意义(P<0.0001);4个激酶unsp、PKC、PKA、CKⅡ能在39个位点将其底物SPP1蛋白磷酸化。结论:生物信息学分析SPP1可作为早期肝细胞癌的潜在诊断指标。其升高可能与SPP1基因组扩增、启动子区去甲基化、转录后miR-146a对其3’-UTR调控、蛋白翻译后磷酸化修饰相关。
Objective:To analyze the expression of SPP1 mRNA and the relationship between SPP1 expression and prognosis in patients with hepatocellular carcinoma(HCC).To predict the mechanisms underlying abnormal expression of SPP1 in HCC.Methods:The expression of SPP1 mRNA and the relationship between SPP1 expression and prognosis in patients with HCC were evaluated by using GEPIA database.SPP1 gene mutations,promoter methylation levels,miRNAs binding to 3’-UTR of SPP1,post-translational modification of proteins were predicted by using cBioPortal,MethHC,GCBI and StarBase,and NetPhos 3.1 Server.Results:SPP1 mRNA was elevated in HCC.The overall prognosis of patients with high SPP1 expression was poor(log-rank P=0.00011).Gene amplification and deep deletion occurred in the genome of SPP1 in HCC.The promoter region of SPP1 was hypo-methylated(P<0.005)which was negatively correlated with SPP1 expression(R=0.650,P<0.0001).MiR-146 a can bind to the 3’-UTR of SPP1 mRNA.The expression of miR-146 a was decreased,and the co-expression between miR-146 a and SPP1 was statistically significant in HCC(P<0.0001).Four kinases including unsp,PKC,PKA,and CKⅡcould phosphorylate the substrate protein SPP1 at 39 sites.Conclusion:SPP1 can be used as a potential diagnostic marker for early HCC.The mechanisms underlying SPP1 elevation may be related to SPP1 gene amplification,promoter demethylation,post-transcriptional regulation by miR-146 a,and post-translational phosphorylation modification.
作者
成镀
谢鹏
操寄望
CHENG Du;XIE Peng;CAO Jiwang(Dept.of Gastroenterology,Renmin Hospital of Wuhan University&Hubei Key Laboratory of Digestive Diseases,Wuhan 430060,Hubei,China)
出处
《武汉大学学报（医学版）》
CAS
2019年第6期886-890,共5页
Medical Journal of Wuhan University
基金
国家自然科学基金青年科学基金项目(编号:81400624).
关键词
SPP1
肝细胞癌
预后
甲基化
磷酸化
SPP1
Hepatocellular Carcinoma
Prognosis
Methylation
Phosphorylation
