Nasopharyngeal carcinoma (NPC) is a common malignant tumor and a major cause of mortality and morbidity in southern China. However, the mechanism is still elusive. Here, we focused on studying the role of squalene epoxidase (SQLE), a key enzyme of cholesterol biosynthesis, in the progression of NPC. Clinical study revealed that SQLE expression was significantly upregulated in NPC tissues compared to normal tissues from mRNA level and patients with high expression of SQLE showed a poor prognosis. In vitro experiments showed that SQLE overexpression led to a significant proliferation of cells whereas SQLE knockdown showed an opposite result. In vivo studies also showed that SQLE promoted tumor growth in nude mice. Further study revealed that SQLE promoted NPC proliferation by cholesteryl ester accumulation instead of cholesterol. Mechanism studies indicated that cholesteryl ester promoted NPC cell proliferation by activating the PI3K/AKT pathway and inhibition of this pathway in SQLE-overexpressed or cholesteryl ester-treated cells resulted in a significant reduction of NPC cell proliferation. These results indicate that the oncogenic effect of SQLE in NPC mainly resulted from cholesteryl ester accumulation and PI3K/AKT is a promising target for NPC with SQLE overexpression.
Keywords: AKT; PI3K; SQLE; cholesterol; cholesteryl ester; nasopharyngeal carcinoma.
© 2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.