Abstract
Nasopharyngeal carcinoma (NPC) demonstrates significant regional differences and a high incidence in Southeast Asia and Southern China. Bactericidal/permeability-increasing-fold- containing family B member 1 (BPIFB1) is a relatively specific and highly expressed protein in the nasopharyngeal epithelium. BPIFB1 expression is substantially downregulated in NPC and is significantly associated with poor prognosis in patients with NPC. However, the specific molecular mechanism by which BPIFB1 regulates NPC is not well understood. In this study, we found that BPIFB1 inhibits vasculogenic mimicry by regulating the metabolic reprogramming of NPC. BPIFB1 decreases GLUT1 transcription by downregulating the JNK/AP1 signaling pathway. Altered glycolysis reduces the acetylation level of histone and decreases the expression of vasculogenic mimicry-related genes, VEGFA, VE-cadherin, and MMP2, ultimately leading to the inhibition of vasculogenic mimicry. To our knowledge, this is the first report on the role and specific mechanism of BPIFB1 as a tumor suppressor gene involved in regulating glycolysis and vasculogenic mimicry in NPC. Overall, these results provide a new therapeutic target for NPC diagnosis and treatment.
Highlights
Nasopharyngeal carcinoma (NPC) exhibits significant regional differences and a high incidence in Southeast Asia and southern China
We show that Bactericidal/permeability-increasing-fold-containing family B member 1 (BPIFB1) plays an important role in regulating vasculogenic mimicry
We show that BPIFB1 can inhibits JNK/AP1 signaling which leads to inhibition of glucose transporter 1 (GLUT1) transcription and glycolysis, resulting in reducing histone H3K27 acetylation and decreasing the expression of vasculogenic mimicry-related vascular endothelial growth factor A (VEGFA), VE-cadherin, and matrix metalloproteinase 2 (MMP2)
Summary
Nasopharyngeal carcinoma (NPC) exhibits significant regional differences and a high incidence in Southeast Asia and southern China. Bactericidal/permeability-increasing-fold-containing family B member 1 (BPIFB1) is a relatively specific and highly expressed protein in the nasopharyngeal epithelium. Accumulating evidence indicates that BPIFB1 is substantially downregulated in NPC and low BPIFB1 is associated with NPC patient’s poor prognosis. The clear molecular mechanism by which BPIFB1 regulates NPC is not well understood
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