Li Yanghua, Man Weiling, Li Xiang, Wu Xiaojie, Cui Yumeng, Chen Shiyun, Li Xianhong, Lin Yanli, Jiang Lihe, Wang Youliang
Medical College, Guangxi University, Nanning, China.
Laboratory of Advanced Biotechnology, Beijing Institute of Biotechnology, Beijing, China.
Cell Death Discov. 2025 May 17;11(1):239. doi: 10.1038/s41420-025-02526-5.
This study aims to explore the molecules that affect the survival of Human Umbilical Vein Endothelial Cells (HUVECs) under hypoxia and their mechanisms of action. In hypoxia, plasmolipin (PLLP) was identified through the screening of CRISPR/Cas9 and small guide RNA (sgRNA) library. Functionally, PLLP knockout led to increase cell proliferation, cellular metabolism, tight junction formation, angiogenesis ability, migration and invasion in hypoxic HUVECs. Furthermore, PLLP knockout countered the inhibitory effects of bevacizumab on HUVECs angiogenesis and cell survival in hypoxic conditions. PLLP knockout was found to modulate the survival of HUVECs in hypoxia by enhancing the phosphorylation of AKT and ERK1/2 proteins. In conclusion, inhibiting the expression of PLLP in HUVECs promotes cell survival and maintenance of cellular functions under hypoxic condition. PLLP plays a crucial role in regulating cell survival in hypoxia through the activation of AKT and ERK1/2 pathways. This study identifies novel molecules that affect HUVECs survival under hypoxic conditions and provides a new possibility for future studies on cell survival under hypoxic conditions.
本研究旨在探索在缺氧条件下影响人脐静脉内皮细胞（HUVECs）存活的分子及其作用机制。在缺氧状态下，通过CRISPR/Cas9和小向导RNA（sgRNA）文库筛选鉴定出了质膜脂蛋白（PLLP）。在功能上，PLLP基因敲除导致缺氧的HUVECs细胞增殖增加、细胞代谢加快、紧密连接形成、血管生成能力、迁移和侵袭能力增强。此外，PLLP基因敲除抵消了贝伐单抗对缺氧条件下HUVECs血管生成和细胞存活的抑制作用。研究发现，PLLP基因敲除通过增强AKT和ERK1/2蛋白的磷酸化来调节缺氧状态下HUVECs的存活。总之，抑制HUVECs中PLLP的表达可促进细胞存活并维持缺氧条件下的细胞功能。PLLP通过激活AKT和ERK1/2途径在调节缺氧条件下的细胞存活中起关键作用。本研究鉴定了在缺氧条件下影响HUVECs存活的新分子，并为未来缺氧条件下细胞存活的研究提供了新的可能性。
