Department of Cardiovascular Surgery, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan Province, China.
Metabolic Vascular Diseases Key Laboratory of Sichuan Province, Luzhou, China.
PLoS One. 2023 Mar 9;18(3):e0281061. doi: 10.1371/journal.pone.0281061. eCollection 2023.
Long noncoding RNAs (lncRNAs) are potential regulators of a variety of cardiovascular diseases. Therefore, there is a series of differentially expressed lncRNAs in pulmonary arterial hypertension (PAH) that may be used as markers to diagnose PAH and even predict the prognosis. However, their specific mechanisms remain largely unknown. Therefore, we investigated the biological role of lncRNAs in patients with PAH. First, we screened patients with PAH secondary to ventricular septal defect (VSD) and those with VSD without PAH to assess differences in lncRNA and mRNA expression between the two groups. Our results revealed the significant upregulation of 813 lncRNAs and 527 mRNAs and significant downregulation of 541 lncRNAs and 268 mRNAs in patients with PAH. Then, we identified 10 hub genes in a constructed protein-protein interaction network. Next, we performed bioinformatics analyses, including Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis and subsequently constructed coding-noncoding co-expression networks. We screened lncRNA-TCONS_00008552 and lncRNA-ENST00000433673 as candidate genes and verified the expression levels of the lncRNAs using quantitative reverse-transcription PCR. Although expression levels of lncRNA-TCONS_00008552 in the plasma from the PAH groups were significantly increased compared with the control groups, there was no significant difference in the expression of lncRNA-ENST00000433673 between the two groups. This study bolsters our understanding of the role of lncRNA in PAH occurrence and development and indicates that lncRNA-TCONS_00008552 is a novel potential molecular marker for PAH.
长链非编码 RNA(lncRNA)是多种心血管疾病的潜在调节因子。因此,在肺动脉高压(PAH)中有一系列差异表达的 lncRNA,它们可能作为标志物用于诊断 PAH,甚至预测预后。然而,它们的具体机制在很大程度上仍然未知。因此,我们研究了 lncRNA 在 PAH 患者中的生物学作用。首先,我们筛选了继发于室间隔缺损(VSD)的 PAH 患者和无 PAH 的 VSD 患者,以评估两组之间 lncRNA 和 mRNA 表达的差异。结果显示,PAH 患者中 813 个 lncRNA 和 527 个 mRNA 显著上调,541 个 lncRNA 和 268 个 mRNA 显著下调。然后,我们在构建的蛋白质-蛋白质相互作用网络中确定了 10 个枢纽基因。接下来,我们进行了生物信息学分析,包括基因本体论和京都基因与基因组百科全书通路分析,随后构建了编码-非编码共表达网络。我们筛选了 lncRNA-TCONS_00008552 和 lncRNA-ENST00000433673 作为候选基因,并使用定量逆转录 PCR 验证了 lncRNA 的表达水平。尽管 lncRNA-TCONS_00008552 在 PAH 组血浆中的表达水平明显高于对照组,但两组间 lncRNA-ENST00000433673 的表达无显著差异。这项研究增进了我们对 lncRNA 在 PAH 发生和发展中的作用的理解,并表明 lncRNA-TCONS_00008552 是 PAH 的一个新的潜在分子标志物。