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

Respiratory Research

Huan Liu¹  Yan Lv²  Shuai Guo³  Juan Li⁴  Ming Li⁵ 

[1] College of Life Sciences, Shandong Agricultural University, 271018, Tai’an, China;Department of Internal Medicine Ward IV, Shandong Provincial Chest Hospital, 12# Lieshishandong Road, Jinan, Shandong, China;Department of Medical Oncology, Shandong Provincial Chest Hospital, Jinan, Shandong, China;Department of Pathology, The Third Affiliated Hospital of Shandong First Medical University and The Fourth Hospital of Jinan, Jinan, Shandong, China;Thoracic Surgery, Shandong Provincial Chest Hospital, Jinan, Shandong, China;

关键词: Hypoxia;    NSCLC;    Mitochondrial creatine kinase 1;    HIF-1;    Proliferation;   

DOI  :  10.1186/s12931-021-01765-1

来源: Springer

【 摘 要 】

BackgroundHypoxia 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.MethodsThe mRNA and protein expression of CKMT1 in NSCLC tissues were detected by using GEPIA web, immunohistochemistry and qRT-PCR. For hypoxia, cells were exposed to the 1% O2 atmosphere. The protein levels of HIF-1α and CKMT1 in H1650 and H1299 cells exposed to hypoxia were determined by western blot. The roles of CKMT1 on the proliferation, invasion and hypoxia adaptation of NSCLC cells were measured by CCK8, colony formation and transwell assays. Luciferase activity assay and HIF1 specific inhibitor (LW6) assay indicated the related function of hypoxia and CKMT1.ResultsCKMT1 was highly expressed in NSCLC tissues, and the high level of CKMT1 was significantly correlated with the high pathological grade of NSCLC. Knockdown of CKMT1 inhibited the cell proliferation and invasion of H1650 and H1299 cells, which could be rescued by hypoxia. Hypoxia induced the accumulation of HIF-1α and the expression of CKMT1 in H1650 and H1299 cells. Furthermore, HIF-1 as a transcription factor of CKMT1, could up-regulated the expression of CKMT1 under hypoxia.ConclusionsIn summary, CKMT1 has the potential as a target for NSCLC hypoxic targeted therapy.

【 授权许可】

CC BY