Department of Ultrasound, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, China.
Department of Diagnostic Radiology, Fujian Cancer Hospital of Fujian Medical University, Fuzhou, Fujian, China.
PeerJ. 2023 Feb 27;11:e14962. doi: 10.7717/peerj.14962. eCollection 2023.
Long noncoding RNAs (lncRNAs) have been shown to be involved in the regulation of numerous biological processes in embryonic development. We aimed to explore lncRNA expression profiles in ventricular septal defects (VSDs) and reveal their potential roles in heart development.
Microarray analyses were performed to screen differentially expressed lncRNAs (DE-lncRNAs) and mRNAs (DE-mRNAs) in the amniotic fluid between the VSD group and the control group. Bioinformatics analyses were further used to identify the functional enrichment and signaling pathways of important mRNAs. Then, a coding-noncoding gene coexpression (CNC) network and competitive endogenous RNAs (ceRNA) network were drawn. Finally, qRTPCR was performed to verify several hub lncRNAs and mRNAs in the network.
A total of 710 DE-lncRNAs and 397 DE-mRNAs were identified in the VSD group. GO and KEGG analyses revealed that the DE-mRNAs were enriched in cardiac development-related biological processes and pathways, including cell proliferation, cell apoptosis, and the Sonic Hedgehog signaling pathway. Four VSD related mRNAs was used to construct the CNC network, which included 149 pairs of coexpressing lncRNAs and mRNAs. In addition, a ceRNA network, including 15 lncRNAs, 194 miRNAs, and four mRNAs, was constructed to reveal the potential regulatory relationship between lncRNAs and protein-coding genes. Finally, seven RNAs in the ceRNA network were validated, including IDS, NR2F2, GPC3, LINC00598, GATA3-AS1, PWRN1, and LINC01551.
Our study identified some lncRNAs and mRNAs may be potential biomarkers and therapeutic targets for foetuses with VSD, and described the lncRNA-associated ceRNA network in the progression of VSD.
长链非编码 RNA（lncRNA）已被证明参与胚胎发育过程中许多生物学过程的调控。我们旨在探索室间隔缺损（VSD）患者羊水标本中 lncRNA 的表达谱，并揭示其在心脏发育中的潜在作用。
采用微阵列分析筛选 VSD 组和对照组羊水标本中差异表达的 lncRNA（DE-lncRNA）和信使 RNA（DE-mRNA）。进一步进行生物信息学分析，以鉴定重要 mRNAs 的功能富集和信号通路。然后，构建编码-非编码基因共表达（CNC）网络和竞争内源性 RNA（ceRNA）网络。最后，通过 qRT-PCR 验证网络中的几个关键 lncRNA 和 mRNAs。
在 VSD 组中发现了 710 个 DE-lncRNA 和 397 个 DE-mRNA。GO 和 KEGG 分析表明，DE-mRNAs 富集于心脏发育相关的生物学过程和通路，包括细胞增殖、细胞凋亡和 Sonic Hedgehog 信号通路。选取 4 个与 VSD 相关的 mRNAs 构建 CNC 网络，该网络包括 149 对共表达的 lncRNA 和 mRNAs。此外，构建了 ceRNA 网络，包含 15 个 lncRNA、194 个 miRNA 和 4 个 mRNAs，以揭示 lncRNA 与蛋白质编码基因之间潜在的调控关系。最后，验证了 ceRNA 网络中的 7 个 RNA，包括 IDS、NR2F2、GPC3、LINC00598、GATA3-AS1、PWRN1 和 LINC01551。
本研究鉴定了一些 lncRNA 和 mRNAs 可能是胎儿 VSD 的潜在生物标志物和治疗靶点，并描述了 VSD 进展过程中的 lncRNA 相关 ceRNA 网络。
