医学分子生物学杂志 ›› 2026, Vol. 23 ›› Issue (3): 275-284.doi: 10.3870/j.issn.1672-8009.2026.03.006

• 论著 • 上一篇    下一篇

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

权有武1, 陈元亚1, 吴政杰2, 刘铠雄3, 叶远征4   

  1. 巴楚县人民医院1急诊医学科,2心内科,3肿瘤科 新疆喀什地区,843800
    4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
  • 收稿日期:2025-06-13 发布日期:2026-06-01
  • 通讯作者: 叶远征(E-mail:yeyuanzheng0101@163.com)
  • 基金资助:
    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)

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

QUAN Youwu1, CHEN Yuanya1, WU Zhengjie2, LIU Kaixiong3, YE Yuanzheng4   

  1. 1Department of Emergency Medicine,2Department of Cardiology,3Department of Oncology,People’s Hospital of Bachu County,Kashgar Prefecture,Xinjiang,843800,China
    4Department of Cardiac Function,The First Affiliated Hospital of Xinjiang Medical University,Urumqi,830000,China
  • Received:2025-06-13 Published:2026-06-01
  • Contact: YE Yuanzheng(E-mail:yeyuanzheng0101@163.com)
  • Supported by:
    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)

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 Dnm3osGm13054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。

关键词: 急性冠脉综合征, 转录组测序, 长链非编码RNA, 差异表达基因

Abstract: Objective To identify key molecular biomarkers of acute coronary syndrome(ACS)through transcriptome sequencing and construction of mRNA-lncRNA co-expression networks. Methods An ACS mouse model was established,and the modeling outcomes and cardiac pathological changes were comprehensively evaluated using physiological and pathological assays.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 mitochondrial function,fatty acid metabolism,immune/inflammatory response,cell adhesion,apoptosis,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 DEmRNAs 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 treatment of ACS.

Key words: acute coronary syndrome, transcriptome sequencing, long non-coding RNA, differentially expressed genes

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