Hypoxia-induced CNPY2 upregulation promotes glycolysis in cervical cancer through activation of AKT pathway.

This study aimed to investigate the function and mechanism of the protein-coding gene CNPY2 in the glycolysis of cervical cancer cells. Cells were exposed to normoxia and hypoxia conditions. Knockdown and ectopic overexpression of CNPY2 were achieved by transfection of small interfering RNA (siRNA) specific to CNPY2 or CNPY2 overexpression vectors, respectively. Quantitative real-time PCR and Western blot were used to evaluate CNPY2 expression in patient specimens and different cervical cancer cell lines under normoxia or hypoxia conditions. Cell viability was assessed by MTT and colony formation assays. Glucose consumption, lactate production, oxygen consumption and ATP production were analyzed by enzyme-linked immunosorbent assays. Dual-luciferase reporter assay and chromatin immunoprecipitation assay were performed to detect interaction between hypoxia-induced factor 1α (HIF-1α) on CNPY2 promoter. CNPY2 upregulation was a characteristic of cervical cancer and correlated with poor prognosis. Knockdown and overexpression of CNPY2 inhibited and promoted proliferation glucose consumption, lactate production, oxygen consumption and ATP production in cervical cancer cells, respectively. CNPY2 was transcriptionally regulated by HIF-1α. The hypoxia-induced "Warburg effect" in cervical cancer cells was at least partially dependent on the CNPY2/AKT signaling pathway. Hypoxia-induced CNPY2 promoted glycolysis in cervical cancer cells by activating the AKT pathway. CNPY2 may serve as a potential diagnostic marker and therapeutic target for cervical cancer patients.