Xi Yangbo, Chen Dongping, Dong Zhihui, Lam Hingcheung, He Jiading, Du Keyi, Chen Can, Guo Jun, Xiao Jianmin
Department of The First Clinical Medical College, Jinan University, Guangzhou, China.
Department of Cardiology, The First Affiliated Hospital of Jinan University, Guangzhou, China.
Front Genet. 2022 Apr 13;13:848364. doi: 10.3389/fgene.2022.848364. eCollection 2022.
Diabetic cardiomyopathy (DCM) is one of the major causes of heart failure in diabetic patients; however, its pathogenesis remains unclear. Long non-coding RNAs (lncRNAs) are involved in the development of various cardiovascular diseases, but little is known in DCM. The present study was conducted to investigate the altered expression signature of lncRNAs and mRNAs by RNA-sequencing and uncovers the potential targets of DCM. A DCM rat model was established, and the genome-wide expression profile of cardiac lncRNAs and mRNAs was investigated in the rat model with and without DCM by RNA-sequencing. Bioinformatics analysis included the co-expression, competitive endogenous RNA (ceRNA) network, and functional enrichment analysis of deregulated lncRNAs and mRNAs. A total of 355 lncRNA transcripts and 828 mRNA transcripts were aberrantly expressed. The ceRNA network showed that lncRNA XR_351927.3, ENSRNOT00000089581, XR_597359.2, XR_591602.2, and XR_001842089.1 are associated with the greatest number of differentially expressed mRNAs and AURKB, MELK, and CDK1 may be the potential regulatory targets of these lncRNAs. Functional analysis showed that these five lncRNAs are closely associated with fibration, cell proliferation, and energy metabolism of cardiac myocytes, indicating that these core lncRNAs have high significance in DCM. The present study profiled the DCM-specific lncRNAs and mRNAs, constructed the lncRNA-related ceRNA regulatory network, and identified the potential prognostic biomarkers, which provided new insights into the pathogenesis of DCM.
糖尿病性心肌病(DCM)是糖尿病患者心力衰竭的主要原因之一;然而,其发病机制仍不清楚。长链非编码RNA(lncRNA)参与多种心血管疾病的发生发展,但在DCM中的作用知之甚少。本研究旨在通过RNA测序研究lncRNA和mRNA的表达特征变化,并揭示DCM的潜在靶点。建立了DCM大鼠模型,通过RNA测序研究了有或无DCM的大鼠模型中心脏lncRNA和mRNA的全基因组表达谱。生物信息学分析包括共表达、竞争性内源性RNA(ceRNA)网络以及差异表达的lncRNA和mRNA的功能富集分析。共有355个lncRNA转录本和828个mRNA转录本异常表达。ceRNA网络显示,lncRNA XR_351927.3、ENSRNOT00000089581、XR_597359.2、XR_591602.2和XR_001842089.1与差异表达的mRNA数量最多相关,AURKB、MELK和CDK1可能是这些lncRNA的潜在调控靶点。功能分析表明,这五个lncRNA与心肌细胞的纤维化、细胞增殖和能量代谢密切相关,表明这些核心lncRNA在DCM中具有重要意义。本研究分析了DCM特异性的lncRNA和mRNA,构建了与lncRNA相关的ceRNA调控网络,并确定了潜在的预后生物标志物,为DCM的发病机制提供了新的见解。