Psychological distress promotes proliferation and invasion of glioma by upregulating lactate deoxygenase A

: Objective To investigate the role of lactate deoxygenase A (LDHA) expression in the proliferation and invasion of glioma promoted by the psychological distress. Methods The glioma-bearing nude mice were divided into tumor bearing group, stress tumor bearing group, negative control, short hairpin RNA (shRNA)-lactate dehydrogenase A (LDHA) group and shRNA-LDHA stress group. Four weeks after stress, the tumor size of each group was measured; meanwhile, norepinephrine (NE) andadrenaline (EPI) in the blood were detected by ELISA; lactic acid in the tumor tissue was determined by colorimetry. And the expression level of LDHA was detected by Western blotting. The proliferation of glioma LN229 cells stimulated by NE was detected by CCK-8 assay and plate clone formation assay; TranswellTM assay was used to test the invasive ability of LN229 cells. The level of LDHA mRNA was detected by real-time quantitative PCR. The expressions of LDHA, ERK1/2 and hypoxia-induced factor-1α (HIF-1α) were observed using Western blotting. By constructing the reporter gene, we studied the mechanism of LDHA expression regulated by NE. Results The tumor size and the levels of EPI, NE, lactic acid and LDHA in the stress group significantly increased as compared with the tumor bearing group. After silencing LDHA, the proliferation rate and lactate content decreased. Compared with the control group, the mRNA and protein levels of LDHA in NE group was significantly elevated; the phosphorylation levels of HIF-1α and ERK1/2 was significantly raised; and cell proliferation and invasion ability were also enhanced. Promoter luciferase reporter assay confirmed that NE up-regulated the expression of LDHA by HIF-1α. Conclusion Adverse psychological stress can promote the proliferation and invasion of glioma cells by upregulating LDHA expression.