Pik3ap1-KO Mouse

Pik3ap1, also known as B-cell adapter for PI3K (BCAP), plays a crucial role in the PI3K/AKT signaling pathway [3,5,6,7,8]. It is involved in regulating various biological processes such as immune response, cell proliferation, and macrophage transition, which are vital for maintaining normal physiological functions [1,3,4,5,6,7,8,9].

In macrophage-specific BCAP-deficient mice, they fail to recover from dextran sulfate sodium-induced colitis due to prolonged intestinal inflammation and impaired tissue repair, indicating that Pik3ap1 is essential for the transition of macrophages from an inflammatory to a reparative state [1]. In patients with Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Adenitis (PFAPA) syndrome, the PIK3AP1 gene region shows differential methylation, suggesting its potential role in the etiology of this auto-inflammatory disease [2]. Gastric epithelial cells (GES-1) stimulated by Helicobacter pylori show hypermethylation of the PIK3AP1 promoter, leading to down-regulation of PIK3AP1 expression. Intervention of PIK3AP1 inhibits the expression of downstream gene AKT and the immunoinflammatory gene IL-6, and promotes cell proliferation [3]. Overexpression of PIK3AP1 significantly inhibits African swine fever virus (ASFV) replication in vitro, and this suppressive effect is independent of the PI3K-Akt pathway [4]. In gastric cancer, PIK3AP1 activates AKT phosphorylation, and a miR-567-PIK3AP1-PI3K/AKT-c-Myc feedback loop regulates tumour growth and chemoresistance [5]. In thyroid cancer, miR-1246 targets PIK3AP1 to regulate the PI3K/AKT signaling pathway, inhibiting cell proliferation and tumor growth [6]. In cervical cancer, WT1-AS inhibits the progression of cervical cancer through the SPI1/PIK3AP1 axis [7]. In hepatocellular carcinoma, BRG1 regulates lipid metabolism through the PIK3AP1/PI3K/AKT pathway by mediating GLMP expression [8]. In Behcet's disease, patients with high disease activity have higher expression of PIK3AP1 [9].

In conclusion, Pik3ap1 is a key regulator in the PI3K/AKT signaling pathway, participating in numerous biological processes. Studies using gene-knockout or conditional-knockout mouse models, as well as research on various human diseases, have revealed its significant roles in inflammation, auto-inflammation, virus-host interactions, tumorigenesis, and lipid metabolism. Understanding Pik3ap1 function provides insights into the underlying mechanisms of these biological processes and diseases, potentially guiding the development of new therapeutic strategies.