信号识别颗粒14调控肝细胞癌进程并影响患者预后  

Expression of signal recognition particle 14 in hepatocellular carcinoma and its relationship with disease progression and patient survival

作　　者：田慧敏 唐冬梅[2] 马美琳 傅湘辉[1,4] TIAN Huimin;TANG Dongmei;MA Meilin;FU Xianghui(Department of Endocrinology and Metabolism,Center for Diabetes and Metabolism Research,West China Hospital,Sichuan University,Chengdu 610041,China;Collaborative Innovation Center of Biotherapy,Sichuan University,Chengdu 610041,China;Institute of Metabolic Diseases and Pharmacotherapy,West China Hospital,Sichuan University,Chengdu 610041,China;Department of Biotherapy,West China Hospital,Sichuan University,Chengdu 610041,China)

机构地区：[1]四川大学华西医院内分泌代谢科糖尿病与代谢研究室,四川成都610041 [2]四川大学生物治疗协同创新中心,四川成都610041 [3]四川大学华西医院代谢疾病与药物治疗研究所,四川成都610041 [4]四川大学华西医院生物治疗研究中心,四川成都610041

出　　处：《浙江大学学报（医学版）》2024年第4期460-471,共12页Journal of Zhejiang University(Medical Sciences)

基　　金：四川大学华西医院学科卓越发展1·3·5工程项目(ZYGD23005)。

摘　　要：目的:探究信号识别颗粒14(SRP14)在肝细胞癌(HCC)中的表达及功能。方法:利用生物信息学、定量逆转录聚合酶链反应(qRT-PCR)、免疫组织化学染色和蛋白质印迹法等明确SRP14在HCC中的表达;应用Kaplan-Meier法分析SRP14 mRNA表达变化与HCC患者的总生存期、无进展生存期及疾病特异性生存期的相关性;通过5-乙基-2′-94脱氧尿苷(EdU)染色、MTS实验、Transwell小室实验及细胞划痕实验等探索SRP14对HCC细胞增殖和迁移的作用;利用京都基因与基因组百科全书(KEGG)和基因本体(GO)富集分析以及qRT-PCR初探SRP14在HCC中的作用机制。结果:在GSE14520数据集、TNMplot数据库和临床标本中,与配对癌旁组织、非配对癌旁组织或正常组织比较,HCC组织的SPR14 mRNA表达均有不同程度的升高(均P<0.05)。在临床标本中,与配对癌旁组织比较,HCC组织的SPR14蛋白表达上调(P<0.05)。SRP14表达上调的HCC患者具有更长的总生存期、无进展生存期及疾病特异性生存期(均P<0.05)。细胞实验结果显示,SRP14能抑制HCC细胞的体外增殖和迁移。KEGG和GO富集分析结果显示,在HCC中,与SRP14共表达的基因主要调控蛋白质合成、加工和运输等相关细胞活动或功能;在非酒精性脂肪性肝病相关HCC中,与SRP14共表达的基因主要调控MAPK、cAMP、PI3K-Akt、Wnt等多条信号传导通路。SRP14抑制HCC细胞中已知抑癌基因GPRC5A的mRNA表达(P<0.05)。结论:SRP14可能调控HCC进程并影响患者预后。Objective:To investigate the expression of signal recognition particle 14(SRP14)in hepatocellular carcinoma(HCC)and its clinical significance.Methods:The data of SRP14 expression in HCC were obtained from bioinformatics study,and from investigation with quantitative reverse transcription polymerase chain reaction(qRTPCR),immunohistochemical staining and Western blotting in clinical samples.The Kaplan-Meier analysis was used to determine the associations between SRP14 mRNA expression and the overall survival,progression-free survival,and disease-specific survival of HCC patients.The effect of SRP14 on the proliferation and migration of HCC cells were determined by EdU staining,MTS,Transwell and wound-healing assays.The potential mechanism for SRP14 regulating HCC was explored through Kyoto Encyclopedia of Genes and Genomes(KEGG)and Gene Ontology(GO)enrichment analysis as well as qRT-PCR.Results:According to the data from GSE14520,TNMplot database and clinical samples,compared with paired tumor-adjacent tissues,non-paired tumoradjacent tissues and normal tissues,the mRNA expression of SPR14 in HCC tissues was upregulated(all P<0.05).In clinical samples,compared with paired tumor-adjacent tissues,the protein expression of SPR14 in HCC tissues was increased(P<0.05).The increased mRNA expression of SRP14 was associated with good overall survival,progression-free survival,and disease-specific survival in HCC patients.SRP14 inhibited the proliferation and migration of HCC cells in vitro.According to the KEGG and GO enrichment analysis,in non-specific HCC,the genes co-expressed with SRP14 may predominantly regulate protein synthesis,processing,and transport,while in nonalcoholic fatty liver disease related HCC,the genes co-expressed with SRP14 could control multiple signaling pathways such as MAPK,cAMP,PI3K-Akt,and Wnt.Mechanistically,SRP14 up-regulated the mRNA expression of tumor suppressor gene GPRC5A in HCC cells(P<0.05).Conclusion:SRP14 may regulate HCC progression and influence patient prognosis.

关 键 词：肝细胞癌 非酒精性脂肪性肝病 信号识别颗粒14 G蛋白偶联受体C类组5成员A 细胞增殖 细胞迁移 预后 

分 类 号：R363.2[医药卫生—病理学] R735.7[医药卫生—基础医学]