Mitochondrial creatine kinase 1 in non-small cell lung cancer progression and hypoxia adaptation

Background: Hypoxia is a prominent feature of solid cancer. This research aims to expose the role of mitochondrial creatine kinase 1 (CKMT1) in non-small cell lung cancer (NSCLC) progression and hypoxia adaptation. Methods The mRNA and protein expression of CKMT1 in NSCLC tissues and cells were detected using GEPIA web, immunohistochemistry, qRT-PCR and western blot. Cells were exposed to a hypoxic chamber with atmosphere containing 5% CO 2 , 1% O 2 and residual N 2 . The protein levels of HIF-1α and CKMT1 in H1650 and H1299 cells exposed to hypoxia were determined by western blot. Luciferase activity assay and HIF1 specific inhibitor (LW6) assay indicated the related function of HIF-1 and CKMT1. The role of CKMT1 to NSCLC cells biological function on hypoxic condition was measured by CCK8, colony formation, transwell and apoptosis assay. Results CKMT1 was highly expressed in NSCLC tissues and cells using GEPIA web, immunohistochemistry, qRT-PCR and western blot. Hypoxia induced the accumulation of HIF-1α and the expression of CKMT1 in H1650 and H1299 cells. The results of luciferase activity assay and HIF1 specific inhibitor (LW6) assay indicated that HIF-1, as a transcription factor of CKMT1, up-regulated the expression of CKMT1 under hypoxic conditions. Further, knockdown of CKMT1 inhibited the cell proliferation and invasion of H1650 and H1299 cells, which could be rescued by hypoxia. Conclusions In summary, CKMT1 has the potential as a target for NSCLC hypoxic targeted therapy.