Cheng Long, Zhao Liang, Wang Geng
Department of Anesthesiology, Beijing Jishuitan Hospital, Capital Medical University, Beijing, 100000, China.
Department of Obstetrics and Gynecology, Beijing Jishuitan Hospital, Capital Medical University, Beijing, 100000, China.
Reprod Sci. 2024 Mar;31(3):687-696. doi: 10.1007/s43032-023-01368-9. Epub 2023 Oct 9.
Preeclampsia (PE) belongs to hypertensive disorder complicating pregnancy, which is a serious obstetric complication. Propofol is a new type of fast and short-acting general anesthetic, which has also been demonstrated to promote the cell growth recently. Therefore, this study was carried out to explore the effects of propofol on the cell growth, migration and invasion in the HTR-8/SVneo cells. The cell biological behaviors were analyzed using CCK-8, EdU, transwell assays. The relationship between METTL3 and ZEB2 was confirmed by RIP assay. Western blot and RT-qPCR assays were carried out to detect the protein and mRNA levels. The results showed that propofol enhanced the cell viability, proliferation, migration and invasion of the HTR-8/SVneo cells. Besides, METTL3 overexpression neutralized the propofol role. Furthermore, METTL3 overexpression elevated the m6A levels of ZEB2 and decreased the mRNA levels and stability of ZEB2. ZEB2 overexpression neutralized the role of METTL3 in the propofol treated HTR-8/SVneo cells. In conclusion, this study demonstrated the effects of propofol on promoting the cell growth, migration and invasion of HTR-8/SVneo cells. Mechanistically, propofol indirectly regulated ZEB2 expression by targeting METTL3 mediated m6A methylation modification.
子痫前期(PE)属于妊娠期高血压疾病,是一种严重的产科并发症。丙泊酚是一种新型的速效短效全身麻醉剂,最近也被证明可促进细胞生长。因此,本研究旨在探讨丙泊酚对HTR-8/SVneo细胞生长、迁移和侵袭的影响。使用CCK-8、EdU、transwell实验分析细胞生物学行为。通过RIP实验证实METTL3与ZEB2之间的关系。进行蛋白质免疫印迹法(Western blot)和逆转录-定量聚合酶链反应(RT-qPCR)实验以检测蛋白质和mRNA水平。结果表明,丙泊酚增强了HTR-8/SVneo细胞的活力、增殖、迁移和侵袭能力。此外,METTL3过表达抵消了丙泊酚的作用。此外,METTL3过表达提高了ZEB2的m6A水平,并降低了ZEB2的mRNA水平和稳定性。ZEB2过表达抵消了METTL3在丙泊酚处理的HTR-8/SVneo细胞中的作用。总之,本研究证明了丙泊酚对促进HTR-8/SVneo细胞生长、迁移和侵袭的作用。机制上,丙泊酚通过靶向METTL3介导的m6A甲基化修饰间接调节ZEB2的表达。