基于小鼠肝细胞癌全转录组测序的Ighmbp2表达上调的机制  

Mechanism of upregulated expression of Ighmbp2 in mouse hepatocellular carcinoma based on whole transcriptome sequencing

作　　者：陈峥宇 倪安妮 唐玉莲 孙丽双 李书 刘会婷 罗绿景 李根亮 CHEN Zhengyu;NI Anni;TANG Yulian;SUN Lishuang;LI Shu;LIU Huiting;LUO Lüjing;LI Genliang(Department of Biochemistry and Molecular Biology,School of Basic Medical Sciences,Youjiang Medical University for Nationalities,Baise 533000,China)

机构地区：[1]右江民族医学院基础医学院生物化学与分子生物学教研室,百色533000

出　　处：《山西医科大学学报》2023年第10期1314-1322,共9页Journal of Shanxi Medical University

基　　金：国家自然科学基金资助项目(31760758,31960728)。

摘　　要：目的探讨免疫球蛋白μ结合蛋白2(Ighmbp2)在小鼠肝细胞癌(HCC)中上调表达的可能机制。方法20只小鼠注射生理盐水,收集其肝组织作为SL组。80只小鼠注射H22肝癌细胞系,分别收集注射3 d的小鼠的肝组织、30 d未成瘤小鼠的肝组织及成瘤小鼠的癌旁组织和瘤组织,分别作为H3L组、H30NL组、H30L组和H30T组。采用全转录组测序和生物信息学分析Ighmbp2基因在各组中的表达,并进一步采用华大基因多组学系统筛选差异表达的Ighmbp2相关基因,构建差异表达相关基因的PPI、Target以及ceRNA网络,分析其功能。结果与SL组相比,H3L组、H30NL组、H30L组和H30T组Ighmbp2基因表达均上调,其中H30T组中表达最高;组间比较显示,仅H30T组与其他四组间Ighmbp2基因的表达差异具有统计学意义(P<0.05)。PPI、Target和ceRNA调控网络显示,与Ighmbp2存在密切关系的转录本有5个、基因编码蛋白有43个,互为竞争性ceRNA的分子有143个,其中miR-107-5p、miR-3064-5p和miR-1968-5p在H30T组中的表达显著低于其他各组,转录本XM_006531702.1大量表达于各组,并且在H30T组的表达远高于其他组。GO和KEGG富集分析发现,Ighmbp2及其相关基因共同参与的功能包括核苷酸结合、ATP结合等,其中部分基因与Ighmbp2基因一样属于核、核仁等细胞组分。结论Ighmbp2基因的上调表达主要是转录本XM_006531702.1的上调表达;miR-107-5p、miR-3064-5p和miR-1968-5p这3种miRNA可能在瘤体组织中低表达从而减弱了抑制效应进而间接促进Ighmbp2在瘤体组织中的上调表达,其中miR-1968-5p可能是影响Ighmbp2表达的关键因素,多种相关分子可能与以上3种miRNA结合形成ceRNA调控机制进而进一步精细调控Ighmbp2的表达。Objective To explore the possible mechanism of upregulated expression of immunoglobulin mu-binding protein 2(Ighmbp2)in mouse hepatocellular carcinoma(HCC).Methods Twenty mice were injected with saline and their liver tissues were collected as SL group.Eighty mice were injected with H22 hepatocellular carcinoma cell line,and the liver tissues from mice after injection for 3 d,the liver tissues from tumour-naive mice after injection for 30 d,and the paracarcinoma and tumour tissues from tumour-bearing mice were collected as H3L group,H30NL group,H30L group and H30T group,respectively.Whole transcriptome sequencing and bioinformatics were used to examine Ighmbp2 gene expression in each group.In addition,the UW Genetics Multiomics System was used to identify the differentially expressed Ighmbp2-related genes,and construct PPI,Target and ceRNA networks to investigate their functions.Results Compared with SL group,the expression of Ighmbp2 gene was upregulated in H3L group,H30NL group,H30L group and H30T group,and the expression was the highest in H30T group.Comparison between groups showed that the difference of Ighmbp2 gene expression was statistically significant only between H30T group and the other four groups(P<0.05).A total of five transcripts,43 genetically encoded proteins and 143 molecules with competing ceRNAs were found to be closely associated with Ighmbp2 through the regulatory networks of PPI,Target and ceRNA.Among them,miR-107-5p,miR-3064-5p and miR-1968-5p showed significantly lower expression levels in H30T group compared to the other groups.Transcript XM_006531702.1 was abundantly expressed in all groups and was much higher in H30T group than that in the other groups.GO and KEGG enrichment analyses revealed that Ighmbp2 and its related genes were collectively involved in functions such as nucleotide binding,ATP binding,etc.,and some of these genes belonged to the nucleus,nucleolus and other cellular components such as Ighmbp2 gene.Conclusion The upregulated expression of Ighmbp2 gene is predominantl

关 键 词：肝细胞癌 Ighmbp2 MIRNA ceRNA 全转录组测序 

分 类 号：R735.7[医药卫生—肿瘤]