PIK3R3, a regulatory subunit of phosphatidylinositol 3-kinase (PI3K), plays diverse roles in multiple biological processes. It is involved in pathways such as NF-κB, p53/p21, and Akt signaling, which are crucial for cell growth, senescence, and inflammation regulation. Its abnormal expression is associated with various diseases, making it an important gene for understanding disease mechanisms [1-4].

In inflammatory bowel disease (IBD), PIK3R3 is increased and negatively regulates ZO-1 expression via the NF-κB pathway. Inhibition of PIK3R3 by N15 ameliorates DSS-induced intestinal permeability and IBD symptoms in mouse models, indicating its potential as a therapeutic target for IBD [1].

In colorectal cancer cells, PIK3R3 inhibits cell senescence through the p53/p21 signal pathway by binding to p53 and affecting p21 gene transcription, suggesting it could be a potential tumor therapy target [2].

In liver cancer, PIK3R3 is upregulated, activates Akt signaling, and controls cancer growth by regulating CDKN1C and SMC1A, making targeting it a promising treatment strategy [3].

In summary, PIK3R3 is a key regulatory factor in multiple biological processes and disease conditions. Studies using mouse models, especially those with PIK3R3 inhibition, have revealed its role in IBD, cancer cell senescence, and liver cancer growth, highlighting its potential as a therapeutic target in these disease areas.