心血管衰老时序变化相关miRNA调控基因的差异表达及其功能分析  

Differential expression and functional analysis of miRNA regulatory genes related to temporal changes of cardiovascular aging

作　　者：周靖雅 李鹏[2] 范济瑞 ZHOU Jingya;LI Peng;FAN Jirui(The Fourth Clinical Medical College,the Affiliated Hospital of Traditional Chinese Medicine,Xinjiang Medical University,Urumqi 830000,China;Department of Cardiology,the Affiliated Hospital of Traditional Chinese Medicine,Xinjiang Medical University,Urumqi 830000,China)

机构地区：[1]新疆医科大学第四临床医学院 [2]新疆医科大学附属中医医院心内一科,乌鲁木齐830000

出　　处：《新疆医科大学学报》2025年第4期464-470,共7页Journal of Xinjiang Medical University

基　　金：国家自然科学基金项目(81760883);新疆维吾尔自治区“天山雪松计划”科技创新领军人才后备人选项目(2017XS11)。

摘　　要：目的探讨不同年龄段间心血管衰老相关微小RNA(miRNA)调控基因的差异表达及功能分析。方法筛选2020年1月-2021年1月符合入选标准的临床健康受检者12例,按年龄平均分为3组:≤44岁组、45~59岁组、≥60岁组,利用基因芯片技术筛选组间差异基因,对差异miRNA进行靶基因预测、基因本体论(GO)分析、KEGG信号通路分析。结果(1)与≤44岁组相比,45~59岁组有5个差异miRNA,其中3个miRNA表达上调,2个miRNA表达下调;与≤44岁组相比,≥60岁组有40个差异miRNA,其中20个miRNA表达上调,20个miRNA表达下调。与45~59岁组相比,≥60岁组有38个差异miRNA,其中36个miRNA表达上调,2个miRNA表达下调。(2)45~59岁组与≤44岁组差异miRNA的靶基因有45个,≥60岁组与≤44岁组差异miRNA的靶基因有985个,≥60岁组与45~59岁组差异miRNA的靶基因有1296个。(3)GO和KEGG富集分析结果显示,45~59岁组与≤44岁组差异miRNA的靶基因主要参与调控干细胞增殖以及DNA损伤信号,富集在p53信号通路、脂肪细胞因子信号通路、长寿调节途径等;≥60岁组与≤44岁组差异miRNA的靶基因主要参与细胞黏附,富集在cAMP信号通路等;≥60岁组与45~59岁组差异miRNA的靶基因主要参与葡萄糖转运过程,富集在T细胞受体信号通路、调节干细胞多能性信号通路以及调节昼夜节律途径等。(4)扩大样本量验证结果显示,miR-21-3p在≥60岁组中具有表达上调趋势,miR-338-5p在≥60岁组中具有表达下调趋势,且初步呈现年龄依赖性下降。与≤44岁组比较,≥60岁组磷酸酶和张力蛋白同源基因(PTEN)和沉默信息调节因子1(SIRT1)基因的表达显著下降(P<0.05)。结论miR-21-3p、miR-212-3p、miR-338-5p是心血管衰老时序变化相关的差异miRNA,可能通过调控靶基因PTEN和SIRT1的表达,参与调控血管内皮及心肌细胞周期、细胞衰老与修复及能量代谢等过程,从而影响心血管衰老。Objective To investigate the differential expression and functional analysis of miRNA regulatory genes related to cardiovascular aging in different age groups.Methods 12 clinically healthy subjects who met the selection criteria from January 2020 to January 2021 were screened and divided into 3 groups based on age:≤44 years old group,45-59 years old group and≥60 years old group.Gene chip technology was used to screen for inter group differential genes,and target gene prediction,GO analysis and KEGG signaling pathway analysis were performed on differential miRNAs.Results(1)Compared with age group of≤44 years old,there were 5 differentially expressed miRNAs in the age group of 45-59 years old,of which 3 miRNAs upregulated and 2 miRNAs downregulated.Compared with≤44 year old group,the≥60 year old group had 40 differentially expressed miRNAs,with 20 miRNAs upregulated and 20 miRNAs downregulated.Compared with 45-59 age group,there were 38 differentially expressed miRNAs in the≥60 year old group,of which 36 miRNAs were upregulated and 2 miRNAs were downregulated.(2)There were 45 target genes for differentially expressed miRNAs between the 45-59 age group and the≤44 age group,985 target genes for differentially expressed miRNAs between the≥60 age group and the≤44 age group and 1296 target genes for differentially expressed miRNAs between the≥60 age group and the 45-59 age group.(3)The GO and KEGG enrichment analysis results showed that the target genes of differentially expressed miRNAs between the 45-59 age group and the≤44 age group were mainly involved in regulating stem cell proliferation and DNA damage signals,and were enriched in the p53 signaling pathway,adipocyte cytokine signaling pathway and longevity regulation pathway,etc.The target genes of miRNAs that differ between the≥60 year old group and the≤44 year old group were mainly involved in cell adhesion and enriched in the cAMP signaling pathway.The target genes of miRNAs that differ between the≥60 year old group and the 45-59 yea

关 键 词：心血管衰老 微小RNA 基因芯片 差异表达 

分 类 号：R256.2[医药卫生—中医内科学]