HIF1α/CCL7/KIAA1199 axis mediates hypoxia-induced gastric cancer aggravation and glycolysis alteration.

Gastric cancer is a common digestion tumor with high malignant severity and prevalence. Emerging studies reported C-C motif chemokine ligand 7 (CCL7) as a regulator of various tumor diseases. Our research explored the function and underlying mechanism of CCL7 during gastric cancer development. RT-qPCR, Western blot and other datasets were employed to evaluate CCL7 expression in tissues and cells. Kaplan-Meier and Cox regression analyses were recruited to evaluate the correlations between CCL7 expression and patients' survival or clinical features. A loss-of-function assay was performed to evaluate the function of CCL7 in gastric cancer. 1% O₂ was utilized to mimic hypoxic condition. KIAA1199 and HIF1α were included in the regulatory mechanism. The results showed that CCL7 was up-regulated and its high expression was correlated with poor survival of gastric cancer patients. Depressing CCL7 attenuated proliferation, migration, invasion, and induced apoptosis of gastric cancer cells. Meanwhile, CCL7 inhibition weakened hypoxia-induced gastric cancer aggravation. Besides, KIAA1199 and HIF1α were involved in the mechanism of CCL7-mediated gastric cancer aggravation under hypoxia. Our research identified CCL7 as a novel tumor-activator in gastric cancer pathogenesis and hypoxia-induced tumor aggravation was regulated by HIF1α/CCL7/KIAA1199 axis. The evidence may provide a novel target for gastric cancer treatment.