[1]杨孟涛,汪 艇,杜 伟,等.miR-181b-5p靶向调控SPP1在肝细胞癌中过表达的临床意义及作用机制[J].医学信息,2022,35(24):79-86.[doi:10.3969/j.issn.1006-1959.2022.24.016]
　YANG Meng-tao,WANG Ting,DU Wei,et al.Clinical Significance and Mechanism of miR-181b-5p Targeting to Regulate SPP1 Overexpression in Hepatocellular Carcinoma[J].Journal of Medical Information,2022,35(24):79-86.[doi:10.3969/j.issn.1006-1959.2022.24.016]
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miR-181b-5p靶向调控SPP1在肝细胞癌中过表达的临床意义及作用机制()
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医学信息[ISSN:1006-1959/CN:61-1278/R]

卷:
35卷
期数:
2022年24期
页码:
79-86
栏目:
论著
出版日期:
2022-12-15

文章信息/Info

Title:
Clinical Significance and Mechanism of miR-181b-5p Targeting to Regulate SPP1 Overexpression in Hepatocellular Carcinoma
文章编号:
1006-1959（2022）24-0079-08
作者:
杨孟涛; 汪 艇; 杜 伟; 等
（安徽医科大学附属巢湖医院肝胆外科，安徽 巢湖 238000）
Author(s):
YANG Meng-tao; WANG Ting; DU Wei; et al.
(Department of Hepatobiliary Surgery,Chaohu Hospital of Anhui Medical University,Chaohu 238000,Anhui,China)
关键词:
肝细胞癌; 分泌型磷蛋白1; miR-181b-5p
Keywords:
Hepatocellular carcinoma; SPP1; miR-181b-5p
分类号:
R735.7
DOI:
10.3969/j.issn.1006-1959.2022.24.016
文献标志码:
A
摘要:
目的 探讨miR-181b-5p与分泌型磷蛋白1（SPP1）的关系及SPP1在肝细胞癌中的表达、临床意义、作用机制。方法 首先从Ualcan数据库中筛选出在肝细胞癌中过表达的前25个基因，选取SPP1基因作为研究对象。另检索HPA数据库获得SPP1基因编码的蛋白在肝细胞癌与正常肝脏组织中的表达量，免疫荧光结果明确其在肝细胞癌细胞中的定位。通过Kaplan-Meier plotter数据库分析SPP1表达量与肝细胞癌患者生存及预后的关系。并检索ENCORI数据库中获取靶向调控SPP1基因的miRNAs，筛选出证据最充分的miR-181b-5p作为研究对象。检索Uclcan数据库,获取miR-181b-5p在肝细胞癌中的表达情况。同时在Kaplan-Meier plotter数据库中明确hsa-miR-181b过表达肝细胞癌患者生存及预后的关系。利用GeneMANIA数据库获得SPP1的基因互作图，并筛选出共表达基因。通过Metascape数据库进行功能富集分析预测SPP1在肝细胞癌细胞中的主要功能。最后从CTD数据库中检索能够影响肝细胞癌与SPP1的化学物质。结果 Ualcan数据库中筛选出在肝细胞癌中差异过表达的前25个基因，分别为GPC3、LCN2、SPP1、UBE2C、PTTG1、SFN、MDK、UBE2T、CCNB1、AKR1B1O、NDUFA4L2、NT5DC2、PLVAP、G6PD、PDZK1IP1、CENPW、SPARCL1、SPINK1、UBD、THY1、PTP4A3、TK1、TACC3、GMNN、STMN1；与正常肝脏组织比较，SPP1在肝细胞癌组织及泛癌组织中高表达（P＜0.05）。免疫组化分析显示，SPP1在肝细胞癌组织中高表达，在正常肝脏组织表达较少；免疫荧光分析显示，SPP1主要分布于肝细胞癌细胞的亚单位高尔基体中。肝细胞癌患者中has-miR-181b-5p与SPP1呈正相关（r=0.171，P=9.85e-04）；生存曲线图分析显示，SPP1高表达、miR-181b-5p高表达的肝细胞癌患者生存周期缩短（P＜0.05）。功能富集分析显示，SPP1主要功能为影响细胞的进程、信号传导、发育进程、生物体之间相互作用的生物过程、病毒进程、细胞活动、定位、刺激反应、多细胞进程、代谢过程、免疫系统进程、生物过程的正调控、生物过程的调控、生物过程的负调控等生物学过程。与SPP1互相作用的化学物质共34种，其中31种化学物质可促进SPP1表达，2种化学物质可抑制其表达，1种化学物质的具体影响尚不明确。结论 miR-181b-5p通过靶向调控SPP1基因的表达，从而促进肝细胞癌的进展，同时发现有多种化学物质可以通过影响肝细胞癌中SPP1基因的表达进而对肝细胞癌的发展起到一定的作用。
Abstract:
Objective To investigate the relationship between miR-181b-5p and secreted phosphoprotein 1 (SPP1) and the expression, clinical significance and mechanism of SPP1 in hepatocellular carcinoma.Methods First, the first 25 genes overexpressed in hepatocellular carcinoma were screened from the Ualcan database, and the SPP1 gene was selected as the research object. The expression of SPP1 protein in hepatocellular carcinoma and normal liver tissues was obtained from HPA database, and its localization in hepatocellular carcinoma cells was confirmed by immunofluorescence. The relationship between SPP1 expression and survival and prognosis of patients with hepatocellular carcinoma was analyzed by Kaplan-Meier plotter database. The miRNAs targeting SPP1 gene were obtained from ENCORI database, and miR-181b-5p with the most sufficient evidence was selected as the research object. Uclcan database was searched to obtain the expression of miR-181b-5p in hepatocellular carcinoma. At the same time, the relationship between survival and prognosis of patients with hsa-miR-181 b overexpression in hepatocellular carcinoma was determined in the Kaplan-Meier plotter database. The gene interaction map of SPP1 was obtained by GeneMANIA database, and the co-expressed genes were screened out. Functional enrichment analysis was performed by Metascape database to predict the main function of SPP1 in hepatocellular carcinoma cells. Finally, chemicals that can affect hepatocellular carcinoma and SPP1 were retrieved from the CTD database.Results The top 25 differentially overexpressed genes in hepatocellular carcinoma were screened out in the Ualcan database, which were GPC3, LCN2, SPP1, UBE2 C, PTTG1, SFN, MDK, UBE2T, CCNB1, AKR1B1O, NDUFA4L2, NT5DC2, PLVAP, G6PD, PDZK1IP1, CENPW, SPARCL1, SPINK1, UBD, THY1, PTP4A3, TK1, TACC3, GMNN, STMN1. Compared with normal liver tissues, SPP1 was highly expressed in hepatocellular carcinoma and pan-carcinoma tissues (P<0.05). Immunohistochemical analysis showed that SPP1 was highly expressed in hepatocellular carcinoma tissues and less expressed in normal liver tissues. Immunofluorescence analysis showed that SPP1 was mainly distributed in the subunit Golgi apparatus of hepatocellular carcinoma cells. In patients with hepatocellular carcinoma, has-miR-181b-5p was positively correlated with SPP1 (r=0.171, P=9.85e-04). Survival curve analysis showed that the survival period of hepatocellular carcinoma patients with high expression of SPP1 and high expression of miR-181b-5p was shortened (P<0.05). Functional enrichment analysis showed that the main functions of SPP1 were affecting cell processes, signal transduction, developmental processes, biological processes of interaction between organisms, viral processes, cell activities, localization, stimulus response, multicellular processes, metabolic processes, immune system processes, positive regulation of biological processes, regulation of biological processes, negative regulation of biological processes and other biological processes. There were 34 chemical substances that interact with SPP1, of which 31 chemical substances could promote SPP1 expression, 2 chemical substances could inhibit its expression, and the specific effect of 1 chemical substance was not clear.Conclusion miR-181b-5p promotes the progression of hepatocellular carcinoma by targeting and regulating the expression of SPP1 gene. At the same time, it is found that a variety of chemical substances can play a role in the development of hepatocellular carcinoma by affecting the expression of SPP1.

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更新日期/Last Update: 1900-01-01