B7-H3 promotes proliferation and migration of lung cancer cells by modulating PI3K/AKT pathway via ENO1 activity

Abstract

Background: B7-H3 (CD276) is overexpressed in diverse malignant tumors and plays critical roles in tumorigenesis and metastasis. However, the mechanism of B7-H3 in lung cancer remains unclear. This study aimed to explore the mechanism of interaction between B7-H3 and α-enolase (ENO1) in lung cancer progression. Methods: Tumor Immune Estimation Resource 2.0 (TIMER 2.0) and Gene Expression Profiling Interactive Analysis 2 (GEPIA 2) databases were used to analyze the B7-H3 messenger RNA (mRNA) expression levels in lung cancer. The Kaplan-Meier (KM) plotter was used to analyze the correlation between B7-H3 and prognosis. Immunoprecipitation and glutathione S-transferase (GST) pull-down were used to verify the B7-H3 and ENO1 interaction. Cell counting kit-8 (CCK-8) and wound healing assays were used to investigate the effect of B7-H3 on the lung cancer growth. Results: Based on the public databases, the analysis showed that B7-H3 mRNA expression levels were upregulated and correlated with patient prognosis in lung cancer. By using B7-H3 gain and off cell model, we concluded that B7-H3 overexpression promoted proliferation and migration of SBC5 cells. Subsequently, we found that both B7-H3 and ENO1 knockdown could inhibit cell proliferation and migration, in the meanwhile, and the phosphorylation levels of PI3K-p85α, and AKT were significantly reduced. Interestingly, we determined that B7-H3 regulated ENO1 activity rather than changing its expression levels. Furthermore, we used an AP-III-a4 to block ENO1 activity in the experiments, which attenuated the roles of B7-H3 not only on phosphorylation levels of those molecules, but also on cell growth and migration. Conclusions: B7-H3 directly interacts with ENO1 in lung cancer cells. B7-H3 can promote proliferation and migration of lung cancer cells by modulating PI3K/AKT pathway via ENO1 activity.