Department of Cardiovascular Surgery, The First Hospital of Hebei Medical University, No. 89 Donggang Road, Shijiazhuang, 050031, Hebei, China.
Department of Pediatric Surgery, Shijiazhuang Maternity & Child Healthcare Hospital, No. 9 Jianguo Road, Shijiazhuang, 050051, Hebei, China.
Mol Cell Biochem. 2020 Jan;464(1-2):193-203. doi: 10.1007/s11010-019-03660-2. Epub 2019 Dec 18.
Nuclear-enriched abundant transcript 1 (NEAT1), a vital long noncoding RNA (lncRNA), exhibits the functions in disparate cancers. Nevertheless, the influences of NEAT1 in congenital heart disease (CHD) remain unreported. The research delves into whether NEAT1 affects H9c2 cells apoptosis and autophagy under the hypoxia condition. Overexpressed NEAT1 vector was transfected into H9c2 cells; then, functions of NEAT1 in cell viability, apoptosis, autophagy, PI3K/AKT/mTOR and JAK1/STAT3 pathways were detected in H9c2 cells under hypoxia condition. Expression of NEAT1 and miR-181b in hypoxia and blood samples from CHD was evaluated. After miR-181b inhibitor transfection, functions of miR-181b repression in the above-mentioned cell behavior and PI3K/AKT/mTOR and JAK1/STAT3 pathways were reassessed. Overexpressed NEAT1 clearly allayed hypoxia-triggered H9c2 cells apoptosis and autophagy. The decreased NEAT1 and miR-181b were showcased in hypoxia and blood samples from CHD; meanwhile, elevated miR-181b evoked by overexpressed NEAT1 was observed in hypoxia-managed H9c2 cells. More importantly, miR-181b inhibition obviously overturned the influences of NEAT1 in hypoxia-affected H9c2 cells apoptosis and autophagy. Besides, overexpressed NEAT1 facilitated PI3K/AKT/mTOR and JAK1/STAT3 activations via enhancing miR-181b. The research exposed that NEAT1 eased hypoxia-triggered H9c2 cells apoptosis and autophagy by expediting PI3K/AKT/mTOR and JAK1/STAT3 pathways via elevating miR-181b.
核富集丰富转录本 1（NEAT1）是一种重要的长非编码 RNA（lncRNA），在不同的癌症中发挥作用。然而，NEAT1 在先天性心脏病（CHD）中的影响尚未报道。本研究探讨了 NEAT1 在缺氧条件下是否影响 H9c2 细胞凋亡和自噬。将过表达 NEAT1 载体转染到 H9c2 细胞中；然后，在缺氧条件下检测 NEAT1 对 H9c2 细胞活力、凋亡、自噬、PI3K/AKT/mTOR 和 JAK1/STAT3 通路的影响。评估了缺氧和 CHD 血液样本中的 NEAT1 和 miR-181b 的表达。转染 miR-181b 抑制剂后，重新评估 miR-181b 抑制对上述细胞行为和 PI3K/AKT/mTOR 和 JAK1/STAT3 通路的影响。过表达 NEAT1 明显减轻了缺氧诱导的 H9c2 细胞凋亡和自噬。缺氧和 CHD 血液样本中显示出降低的 NEAT1 和 miR-181b；同时，在缺氧处理的 H9c2 细胞中观察到过表达 NEAT1 引起的 miR-181b 升高。更重要的是，miR-181b 抑制明显逆转了 NEAT1 在缺氧影响的 H9c2 细胞凋亡和自噬中的作用。此外，过表达 NEAT1 通过增强 miR-181b 促进了 PI3K/AKT/mTOR 和 JAK1/STAT3 的激活。研究表明，NEAT1 通过升高 miR-181b 促进 PI3K/AKT/mTOR 和 JAK1/STAT3 通路，从而减轻缺氧诱导的 H9c2 细胞凋亡和自噬。
