Targeting HLA-F suppresses the proliferation of glioma cells via a reduction in hexokinase 2-dependent glycolysis

HLA-F, a nonclassical HLA class I molecule, is required for regulating immune tolerance.In recent years, HLA-F has been found to play a role in a variety of cancers, including glioma (GM).Additionally, high expression of HLA-F predicts the poor overall survival of individuals with GM.However, the functions of HLA-F in GM remain to be further elucidated.In this study, we found that HLA-F expression was elevated in GM tissues.High levels of HLA-F resulted in a high cell proliferation index and predicted GM recurrence.Forced expression of HLA-F promoted the growth of murine C8-D1A cells transplanted in immunodeficient Rag2 -/-mice.In contrast, silencing HLA-F inhibited cell growth in vitro.Furthermore, targeting HLA-F with an anti-HLA-F antibody suppressed the growth of C8-D1A cells stably expressing HLA-F transplanted in immunodeficient Rag2 -/-mice.In further experiments, we found that forced expression of HLA-F contributed to the aerobic glycolysis phenotype in C8-D1A cells along with an increase in HK2 protein stabilization.Conversely, silencing HK2 by shRNA reduced HLA-F-mediated glycolysis and cell proliferation.Our data indicated that HLA-F promoted cell proliferation via HK2-dependent glycolysis.HLA-F could be a potential therapeutic target for the treatment of GM.