Hypoxia-induced OSBPL10 accelerates pancreatic cancer progression through CNBP sequestration

Abstract

Purpose Given oxysterol binding protein like 10’s (OSBPL10) known involvement in lipid transport and oncogenic activity in other tumors, we aimed to elucidate the mechanism underlying its contribution to pancreatic cancer progression. Methods We employed data from the Gene Expression Omnibus database. A series of assays, including CCK8,colony formation,wound healing and transwell, were conducted to assess the impact of OSBPL10 on the proliferation and metastatic capacities of pancreatic cancer cells. Flow cytometry was employed to evaluate the influence of OSBPL10 on macrophages. Co-immunoprecipitation , mass spectrometry, and western blot assays were utilized to investigate the potential mechanisms of OSBPL10 activity. Results The study revealed a significant uoregulation of OSBPL10 in pancreatic cancer cells, correlating with poor prognosis. OSBPL10 knockdown attenuated pancreatic cancer cells proliferation and metastasis, while its overexpression enhanced these malignant behaviors. Notably, OSBPL10 knockdown promoted the transformation of M2 macrophages into M1 macrophages in the pancreatic cancer microenvironment. Mechanistically, hypoxia-induced upregulation of OSBPL10 through interaction with hypoxia-inducible factor 1-α in the promoter region was identified. Additionally, OSBPL10 directly bound to CNBP, mediating CNBP expression and ultimately regulating the proliferation and metastasis capacity of pancreatic cancer cells, as well as influencing macrophage polarization. Conclusions This study provides comprehensive insights into oncogenic role of OSBPL10 in pancreatic cancer, uncovering key mechanisms involving hypoxia, HIF-α,and CNBP. The finding suggest that OSBPL10 plays s crucial role in promoting pancreatic cancer progression, making it a potential therapeutic target for intervention in this malignancy.