miR-328-3p调控Hspg2参与HCC发生发展研究  

Research on the involvement of miR-328-3p in regulating Hspg2 in the occurrence and development of HCC

作　　者：李书 唐玉莲[2] 孙丽双 李根亮[3] Li Shu;Tang Yulian;Sun Lishuang;Li Genliang(Graduate School,Youjiang Medical University for Nationalities,Baise 533000,Guangxi,China;School of Laboratory Medicine,Youjiang Medical University for Nationalities,Baise 533000,Guangxi,China;School of Basic Medicine,Youjiang Medical University for Nationalities,Baise 533000,Guangxi,China)

机构地区：[1]右江民族医学院研究生学院,广西百色533000 [2]右江民族医学院医学检验学院,广西百色533000 [3]右江民族医学院基础医学院,广西百色533000

出　　处：《右江民族医学院学报》2023年第5期715-721,共7页Journal of Youjiang Medical University for Nationalities

基　　金：百色市科技计划项目区域多发病联合专项(百科20224148)。

摘　　要：目的为了探讨硫酸乙酰肝素蛋白聚糖2(heparan sulfate proteoglycan 2,Hspg2)在肝细胞癌(hepatocellular carcinoma,HCC)中过表达的可能机制。方法通过构建小鼠HCC模型,收集注射H223~5 d小鼠的肝组织、30~40 d未成瘤小鼠的肝组织、30~40 d成瘤小鼠的肝组织和瘤组织,以及注射生理盐水的对照组小鼠的肝组织。基于全转录组测序和实时荧光定量PCR(real-time fluorescence quantitative PCR,RT-qPCR),分析Hspg2 mRNA在不同发展阶段瘤体的相对表达情况,筛选出参与调控Hspg2表达的miRNA和竞争性结合的RNA分子。结果与对照组相比,HCC组织中Hspg2过表达同时与3个转录本存在差异表达(q<0.05,n=3),尤其转录本XM_006538575.1在各样本中都有表达且相对其它2个转录本表达量明显。Hspg2与相关基因形成网络互作或是和各类RNA分子形成ceRNA调控网络。Hspg2连同相关基因共同参与的功能包括细胞基质黏附的胶原蛋白结合,层粘连蛋白结合和信号受体结合等。其中部分基因与Hspg2基因一样也属于基底膜和细胞外基质等细胞组分。结论Hspg2基因在HCC中的过表达主要是转录本XM_006538575.1的过表达,miR-328-3p可能是促进其在HCC组织中高表达的关键因素,多种Hspg2相关基因在HCC组织中与Hspg2互为ceRNA,进一步精细调控其表达。Hspg2与相关基因的编码蛋白一起在细胞基质和细胞外基质通过参与细胞基质黏附的胶原蛋白结合,与层粘连蛋白结合和细胞外基质的成分结合等生物学过程促进HCC的发生发展。Objective To investigate the potential mechanism underlying the overexpression of heparan sulfate proteoglycan 2(Hspg2)in hepatocellular carcinoma(HCC).Methods A mouse HCC model was established,and liver tissues were collected from mice at different stages:those injected with H22 for 3~5 days,those without tumor formation for 30~40 days,those with tumor formation for 30~40 days,and those injected with normal saline(control group).The study analyzed the relative expression levels of Hspg2 mRNA during different stages of tumor development using whole transcriptome sequencing and real-time fluorescence quantitative PCR(RT-qPCR).Additionally,the study screened for miRNAs and competing endogenous RNA molecules involved in regulating Hspg2 expression.Results Hspg2 overexpression in HCC tissues showed differential expression with three transcripts compared to the control group(q<0.05,n=3).Particularly,transcript XM_006538575.1 was consistently expressed in all samples and significantly more expressed than the other two transcripts.Hspg2 interacted with related genes and formed ceRNA regulatory networks with various RNA molecules.The functions of Hspg2 and its related genes included binding to collagen,laminin and signal receptors in cell matrix adhesion.Some of these genes were the same as Hspg2 gene that belong to the basement membrane and extracellular matrix cell components.Conclusion The overexpression of Hspg2 in HCC is primarily attributed to the overexpression of transcript XM_006538575.1.miR-328-3p appears to be a key factor in promoting its high expression in HCC tissues.Several Hspg2-related genes interact with Hspg2 as ceRNAs in HCC tissues,further fine-tuning their expression.Hspg2 and its related genes encoding proteins collectively participate in the collagen binding of cell matrix adhesion,laminin binding,and binding to extracellular matrix components within the cell matrix and extracellular matrix,promoting the development of HCC.

关 键 词：肝肿瘤 硫酸乙酰肝素蛋白聚糖2 转录本 

分 类 号：R735.7[医药卫生—肿瘤]