lncRNA-TCONS_00008552 expression in patients with pulmonary arterial hypertension due to congenital heart disease

PLOS ONE RESEARCH ARTICLE lncRNA-TCONS_00008552 expression in patients with pulmonary arterial hypertension due to congenital heart disease Qi Yang1,2,3☯, Wei Fan1,2,3☯, Banghui Lai1,2,3, Bin Liao1,2,3*, Mingbin Deng ID1,2,3* 1 Department of Cardiovascular Surgery, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan Province, China, 2 Metabolic Vascular Diseases Key Laboratory of Sichuan Province, Luzhou, China, 3 Key Laboratory of Medical Electrophysiology, Ministry of Education & Medical Electrophysiological Key Laboratory of Sichuan Province, (Collaborative Innovation Center for Prevention of Cardiovascular Diseases) Institute of Cardiovascular Research, Southwest Medical University, Luzhou, China a1111111111 a1111111111 a1111111111 a1111111111 a1111111111 ☯ These authors contributed equally to this work. * (BL); (MD) Abstract OPEN ACCESS Citation: Yang Q, Fan W, Lai B, Liao B, Deng M (2023) lncRNA-TCONS_00008552 expression in patients with pulmonary arterial hypertension due to congenital heart disease. PLoS ONE 18(3): e0281061. https://doi.org/10.1371/journal. pone.0281061 Editor: Laszlo Farkas, Ohio State University, UNITED STATES Received: July 24, 2022 Accepted: January 16, 2023 Published: March 9, 2023 Peer Review History: PLOS recognizes the benefits of transparency in the peer review process; therefore, we enable the publication of all of the content of peer review and author responses alongside final, published articles. The editorial history of this article is available here: https://doi.org/10.1371/journal.pone.0281061 Copyright: © 2023 Yang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All relevant data are within the paper and its Supporting Information files. 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. Introduction Pulmonary Arterial Hypertension (PAH) is a fatal disease caused by increased blood flow in the pulmonary circulation [1, 2]. The lesion covers the entire vascular layer and is PLOS ONE | https://doi.org/10.1371/journal.pone.0281061 March 9, 2023 1 / 15 PLOS ONE Funding: This work was financially supported by the National Natural Science Foundation of China (82070277), grant recipient (Bin Liao); the Scientific Research Project of Southwest Medical University (2021ZKQN100); grant recipient (Qi Yang); the Scientific Research Project of Southwest Medical University (2021ZKMSO21), grant recipient (Mingbin Deng). Competing interests: The authors have declared that no competing interests exist. lncRNA-TCONS_00008552 expression in patients with pulmonary arterial hypertension characterised by the gradual increase of pulmonary vascular resistance and pulmonary small vascular plexus lesions, which progressively lead to right-heart hypertrophy and ultimately death due to right-sided heart failure [3]. Currently, there is no specific cure for PAH. The existing molecular targeted drugs, such as endothelin receptor antagonists, phosphodiesterase inhibitors, calcium channel blockers and cyclic prostaglandin analogues, have been reported to achieve certain curative effects in clinical treatment but are unable to curb further deterioration of the condition [4, 5]. PAH pathogenesis is a complex and multifactorial process [6]. Thus, clarification of the molecular mechanism of occurrence and development of PAH and the detection of new molecular markers for early diagnosis, prognosis and therapeutic targets are crucial. In recent years, long noncoding RNAs (lncRNAs), which are noncoding RNA molecules exceeding 200 nucleotides, have become the focus of medical research [7]. They have been demonstrated as involved in important mechanisms through epigenetic, transcriptional activation, transcriptional inhibition, post-transcriptional regulation, intranuclear transport and other pathways [8–10]. In this complex regulatory role, lncRNAs are mainly involved in the mechanism of competitive endogenous RNA [11]. As a molecular sponge of microRNA (miRNA), lncRNAs indirectly regulate the expression of the miRNA target gene by competitively binding miRNA [3, 12]. The abnormal expression of gene products caused by the change in lncRNA levels is associated with the occurrence and development of cardiovascular disease, which has been confirmed by an increasing number of experimental studies [13–15]. For example, plasma or serum samples from people with atherosclerotic disease show increased levels of lncRNA H19 [16, 17]. Gu et al. [18] identified 185 significantly different lncRNAs in chronic thromboembolic pulmonary hypertension tissues by chip analysis, the most notable of which were NR_036693, NR_027783, NR_033766 and NR_001284. Additionally, lncRNAs induced by platelet-derived growth factor BB modulated the proliferation of pulmonary artery smooth muscle cells (PASMCs) [4]. Furthermore, Liu et al. identified 36 upregulated and 111 downregulated lncRNAs in hypoxic pulmonary artery tissue in a hypoxia-induced PAH model and focused on the role and mechanism of lncRNA TCNS-00034812 in the proliferation and apoptosis of PASMCs [19]. Although several studies suggest that lncRNAs play a crucial role in PAH pathogenesis, the role of lncR (...truncated)