首页|期刊导航|医学分子生物学杂志|长链非编码RNA与mRNA调控网络参与急性冠脉综合征发病进程并影响关键信号通路

长链非编码RNA与mRNA调控网络参与急性冠脉综合征发病进程并影响关键信号通路OA

Long Non-Coding RNA-mRNA Regulatory Networks Involved in the Pathogenesis of Acute Coronary Syndrome and Their Impact on Key Signaling Pathways

中文摘要英文摘要

目的 基于急性冠脉综合征(acute coronary syndrome,ACS)小鼠模型,探索 ACS 病变过程中具有关键调控功能的分子标志物,并构建 ACS 病变相关的分子调控网络.方法 本研究构建 ACS 小鼠动物模型,包括中度(ACS-M)和重度(ACS-S)模型,并全面评估 ACS 小鼠的造模结果和心脏病理改变.借助转录组测序获得 ACS 病变所引起的差异表达基因(differentially expressed genes,DEGs),包括长链非编码RNA(long non-coding RNA,lncRNA),最后构建差异 lncRNA 和 mRNA 的分子调控网络.结果 ACS 造模后,HE 染色、TTC 染色和多普勒超声等实验结果均表明 ACS 导致了小鼠心脏组织病理学改变和功能障碍;RNA-seq 结果揭示了 2 557 个 DEGs 在 ACS-M 和 ACS-S 中共上调表达,1 930 个 DEGs 共下调表达,包括mRNA 和 lncRNA.进一步的 GO 功能富集分析结果揭示这些差异 lncRNA 调控线粒体功能、脂肪酸代谢、免疫/炎症反应、细胞粘附、凋亡、纤维化等相关靶基因的差异表达.同时鉴定到 6 种和 ACS 紧密相关的表达模式.其中 lncRNA Dnm3os 和 Gm13054 在 ACS 中持续高表达,并用 RT-qPCR 方法验证其高表达特征;其下游靶标与线粒体功能和组织纤维化密切相关.Gm13054 同时具有调控 Nppa 表达的潜在功能.结论 本研究通过 ACS 样本的 RNA-seq 鉴定出大量差异表达的 mRNA 和 lncRNA,其潜在功能与 ACS 密切相关.同时,mRNA-lncRNA 共表达网络的构建为 ACS 的诊治提供了潜在的靶点和临床应用研究基础.

Objective To identify key molecular biomarkers of acute coronary syndrome(ACS)through transcriptome sequencing and construction of mRNA-lncRNA co-expression net-works.Methods An ACS mouse model was established,and the modeling outcomes and cardiac pathological changes were comprehensively evaluated using physiological and pathological as-says.RNA sequencing(RNA-seq)was performed to obtain gene expression profiles across different samples.Bioinformatics analysis was then applied to explore gene expression changes and functional signaling pathways associated with ACS.Results After ACS modeling,experimental results such as HE staining,TTC staining,and Doppler ultrasound all indicated that ACS led to histopathological changes and dysfunction in mouse cardiac tissue.RNA-seq results revealed 2 557 DEGs that were co-upregulated in both ACS-M and ACS-S,and 1 930 DEGs that were co-downregulated,including mRNAs(DEmRNAs)and lncRNAs(DElncRNAs).Further GO functional enrichment analysis showed that these DElncRNAs regulated the differential expression of target genes related to mito-chondrial function,fatty acid metabolism,immune/inflammatory response,cell adhesion,apopto-sis,fibrosis,and other functions.Additionally,six expression patterns closely associated with ACS were identified.Among them,lncRNAs Dnm3os and Gm13054 were persistently highly expressed in ACS and their high expression characteristics were validated by RT-qPCR.Their downstream targets were closely related to mitochondrial function and tissue fibrosis.Gm13054 also exhibited potential regulatory functions for Nppa expression.Conclusion This study identified a large number of DEm-RNAs and DElncRNAs through RNA-seq,which have potential functions tightly associated with ACS.The construction of a co-expression network between mRNAs and lncRNAs provides potential therapeutic targets and a foundational basis for further clinical research on the diagnosis and treat-ment of ACS.

权有武;陈元亚;吴政杰;刘铠雄;叶远征

巴楚县人民医院 急诊医学科 新疆 喀什地区,843800巴楚县人民医院 急诊医学科 新疆 喀什地区,843800巴楚县人民医院 心内科 新疆 喀什地区,843800巴楚县人民医院 肿瘤科 新疆 喀什地区,843800新疆医科大学第一附属医院心血管病中心心功能科 乌鲁木齐市,830000

医药卫生

急性冠脉综合征转录组测序长链非编码RNA差异表达基因

acute coronary syndrometranscriptome sequencinglong non-coding RNAdif-ferentially expressed genes

《医学分子生物学杂志》 2026 (3)

275-284,10

省部共建中亚高发病成因与防治国家重点实验室-巴楚县人民医院联合项目开放课题(No.SKL-HIDCA-2022-BC3) This work was supported by a grant from the Open Project of the Joint Program of State Key Laboratory of Pathogenesis,Prevention and Treatment of High Incidence Diseases in Central Asia(jointly established by the Ministry and the Province)-Bachu County People's Hospital(No.SKL-HIDCA-2022-BC3).

10.3870/j.issn.1672-8009.2026.03.006

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