Department of Pediatrics, Jining No. 1 People's Hospital, Jining 272011, Shandong, China.
Neonatal Ward, Jining No. 1 People's Hospital, Jining 272011, Shandong, China.
Int J Biol Macromol. 2019 Jan;121:546-555. doi: 10.1016/j.ijbiomac.2018.10.033. Epub 2018 Oct 10.
LncRNA H19 has been widely reported to be up-regulated upon hypoxia. We aimed to uncover the function and mechanism of lncRNA H19 in hypoxic PC-12 cells. Neural-like PC-12 cells were exposed to hypoxia to stimulating an in vitro model of hypoxic brain damage. The expression levels of lncRNA H19 in PC-12 cells were altered by transfection, then cell viability, migration and apoptosis were assessed respectively. Moreover, the cross-regulation between lncRNA H19, miR-28 and SP1 was studied to reveal one of the possible mechanisms of lncRNA H19's function. We found that hypoxia induced remarkable decreases in cell viability and migration, and induced a notable increase in cell apoptosis. Hypoxia-induced cell damage was aggravated by lncRNA H19 overexpression, while was alleviated by lncRNA H19 silence. miR-28 was negatively regulated by lncRNA H19, and SP1 was a target gene of miR-28. Furthermore, lncRNA H19 down-regulated miR-28 expression, which in turn preventing SP1 from degradation by miR-28, and ultimately deactivated PDK/AKT and JAK/STAT signaling pathways. In conclusion, our research demonstrated a protective role of lncRNA H19 silence in hypoxic PC-12 cells. A possible mechanism of which lncRNA H19 functioned to PC-12 cells was that lncRNA H19 down-regulated miR-28 expression, preventing SP1 exhausted by miR-28.
长链非编码 RNA H19 在缺氧时广泛被报道呈上调表达。我们旨在揭示长链非编码 RNA H19 在缺氧 PC-12 细胞中的功能和作用机制。将神经样 PC-12 细胞暴露于缺氧条件下，以刺激体外缺氧性脑损伤模型。通过转染改变 PC-12 细胞中长链非编码 RNA H19 的表达水平，然后分别评估细胞活力、迁移和凋亡。此外，研究了长链非编码 RNA H19、miR-28 和 SP1 之间的相互调控关系，以揭示长链非编码 RNA H19 功能的可能机制之一。我们发现，缺氧诱导细胞活力和迁移显著下降，细胞凋亡显著增加。长链非编码 RNA H19 的过表达加重了缺氧诱导的细胞损伤，而长链非编码 RNA H19 的沉默则减轻了这种损伤。miR-28 受长链非编码 RNA H19 的负调控，而 SP1 是 miR-28 的靶基因。此外，长链非编码 RNA H19 下调 miR-28 的表达，从而阻止 miR-28 对 SP1 的降解，最终使 PDK/AKT 和 JAK/STAT 信号通路失活。综上所述，我们的研究表明长链非编码 RNA H19 的沉默在缺氧 PC-12 细胞中具有保护作用。长链非编码 RNA H19 作用于 PC-12 细胞的一种可能机制是，长链非编码 RNA H19 下调 miR-28 的表达，阻止 miR-28 对 SP1 的消耗。
