Nxph4, also known as neurexophilin 4, is a neuropeptide-like glycoprotein [4,5]. Although its precise physiological function is not fully understood, studies have associated it with multiple biological processes. In the context of cancer, it may be involved in metabolic pathways, cell cycle regulation, and immune-related pathways [4,5,6].

In cancer research, knockdown of Nxph4 significantly suppresses the proliferation, invasion, and migration of colon cancer cell lines HT-29 and HCT116 [1]. In colorectal cancer, overexpression of Nxph4 is associated with unfavorable prognoses, and it promotes malignant tumor progression by inhibiting HIF1A degradation [2]. In bladder cancer, Nxph4 promotes cell proliferation, migration, invasion, and gemcitabine resistance by enhancing reactive oxygen species and glycolysis activation through modulating NDUFA4L2 [3]. In hepatocellular carcinoma, increased Nxph4 expression predicts unfavorable prognosis, and its knockdown suppresses cell proliferation, migration, and invasion [4]. In non-small cell lung cancer, knockdown of Nxph4 inhibits cell proliferation and migration, causing cell cycle arrest [5]. In colon adenocarcinoma, high expression of Nxph4 is associated with poor prognosis, metabolic reprogramming, and immune infiltration [6]. In bladder cancer, Nxph4 is highly expressed, and patients with high Nxph4 expression have shorter overall and progression-free survival, and it is associated with immune infiltration [7].

In conclusion, Nxph4 plays a significant role in promoting the progression of various cancers, including colon, colorectal, bladder, hepatocellular, and non-small cell lung cancers. Loss-of-function experiments, such as knockdown in cell lines, have been crucial in revealing its oncogenic role in these cancer types, providing potential therapeutic targets for cancer treatment.