State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing, Jiangsu 211166, P.R. China.
Department of Gynecology and Obstetrics, Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, Jiangsu 210004, P.R. China.
Mol Med Rep. 2022 Aug;26(2). doi: 10.3892/mmr.2022.12766. Epub 2022 Jun 8.
Macrosomia is a common perinatal complication, with a series of adverse effects on newborns and pregnant women. However, the effects of long non‑coding RNAs (lncRNAs) on non‑diabetic fetal macrosomia (NDFMS) remain unclear. The aim of the present study was to investigate whether aberrant lncRNA expression in the placenta is involved in the pathogenesis of NDFMS and to elucidate its biological mechanisms. The expression profile of lncRNAs in the placentas of pregnant women with NDFMS was investigated using an Agilent Human LncRNA Microarray. Differentially expressed lncRNAs were selected for validation using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). Additionally, the function of lncRNA ubiquitin‑specific peptidase 2 antisense RNA 1 () was investigated using a trophoblast cell line. The results revealed that 763 lncRNAs were upregulated and 129 lncRNAs were downregulated in the placentas of women in the NDFMS group (|FC| ≥2.0). A total of 10 lncRNAs (|FC| ≥4.0, signal value ≥50) were selected for validation using two‑stage RT‑qPCR, indicating that the expression trends of the 10 differentially expressed lncRNAs in the NDFMS group (n=8 vs. 8 and 48 vs. 48) were consistent with the microarray data. In addition, a significant downregulation in the levels of lncRNA was observed in both the microarray data and second‑stage verification. The overexpression of lncRNA induced G1 phase cell cycle arrest and the number of cells entering S phase was reduced. In addition, the viability of HTR‑8/SVneo cells was significantly inhibited when lncRNA was overexpressed. Therefore, these findings demonstrated that lncRNAs were significantly differentially expressed in the placentas of pregnant women with NDFMS and that the downregulation of lncRNA may be involved in the pathogenesis of NDFMS, by promoting trophoblast cell viability.
巨大儿是一种常见的围产期并发症，对新生儿和孕妇有一系列不良影响。然而，长链非编码 RNA（lncRNA）对非糖尿病胎儿巨大儿（NDFMS）的影响尚不清楚。本研究旨在探讨胎盘异常表达的 lncRNA 是否参与 NDFMS 的发病机制，并阐明其生物学机制。采用 Agilent Human LncRNA Microarray 检测 NDFMS 孕妇胎盘 lncRNA 的表达谱。选择差异表达的 lncRNA 进行逆转录-定量聚合酶链反应（RT-qPCR）验证。此外，采用滋养细胞系研究 lncRNA 泛素特异性肽酶 2 反义 RNA 1 () 的功能。结果显示，NDFMS 组胎盘中有 763 个 lncRNA 上调，129 个 lncRNA 下调（|FC|≥2.0）。采用两步 RT-qPCR 对 10 个 lncRNA（|FC|≥4.0，信号值≥50）进行验证，结果表明，NDFMS 组 10 个差异表达 lncRNA 的表达趋势（n=8 与 8，n=48 与 48）与微阵列数据一致。此外，微阵列数据和第二阶段验证均显示 lncRNA 的表达水平显著下调。lncRNA 过表达诱导 G1 期细胞周期阻滞，进入 S 期的细胞数量减少。此外，lncRNA 过表达显著抑制 HTR-8/SVneo 细胞的活力。因此，这些发现表明，NDFMS 孕妇胎盘 lncRNA 表达显著差异，lncRNA 的下调可能通过促进滋养细胞活力参与 NDFMS 的发病机制。
