Luo Honglin, Zhang Yongde, Deng Yanfei, Li Lequn, Sheng Zhaoan, Yu Yanling, Lin Yong, Chen Xiaohan, Feng Pengfei
Guangxi Key Laboratory for Aquatic Genetic Breeding and Healthy Aquaculture, Guangxi Academy of Fishery Sciences, Nanning, China.
Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China.
Front Cell Dev Biol. 2021 Oct 11;9:728821. doi: 10.3389/fcell.2021.728821. eCollection 2021.
Precise regulation of angiogenesis is required for organ development, wound repair, and tumor progression. Here, we identified a novel gene, (New XingHuo light), that is conserved in vertebrates and that plays a crucial role in vascular integrity and angiogenesis. Bioinformatic analysis uncovered its essential roles in development based on co-expression with several key developmental genes. Knockdown of in zebrafish causes global and pericardial edema, loss of blood circulation, and vascular defects characterized by both reduced vascularization in intersegmental vessels and decreased sprouting in the caudal vein plexus. The gene also affects human endothelial cell behavior . We found that functions in part by targeting VE-PTP through interaction with NCL (nucleolin). Loss of (a VE-PTP ortholo) in zebrafish resulted in defects similar to knockdown. Moreover, deficiency attenuates tumor invasion and proteins (including VE-PTP and NCL) associated with angiogenesis and EMT. These findings illustrate that can regulate angiogenesis via a novel -NCL-VE-PTP axis, providing a new therapeutic target for modulating vascular formation and function, especially for cancer treatment.
器官发育、伤口修复和肿瘤进展都需要精确调节血管生成。在这里，我们鉴定出一个新基因（新星火之光），它在脊椎动物中保守，并且在血管完整性和血管生成中起关键作用。生物信息学分析基于其与几个关键发育基因的共表达揭示了它在发育中的重要作用。在斑马鱼中敲低该基因会导致全身性和心包水肿、血液循环丧失以及血管缺陷，其特征是节间血管血管化减少和尾静脉丛芽生减少。该基因也会影响人类内皮细胞行为。我们发现该基因部分通过与NCL（核仁素）相互作用靶向VE-PTP发挥作用。在斑马鱼中缺失（一种VE-PTP同源物）会导致与敲低该基因类似的缺陷。此外，该基因缺陷会减弱肿瘤侵袭以及与血管生成和上皮-间质转化相关的蛋白质（包括VE-PTP和NCL）。这些发现表明该基因可通过一种新的-NCL-VE-PTP轴调节血管生成，为调节血管形成和功能，尤其是癌症治疗提供了一个新的治疗靶点。
