Thoracic Surgery, Shandong Provincial Chest Hospital, Jinan, Shandong, China.
College of Life Sciences, Shandong Agricultural University, Tai'an, 271018, China.
Respir Res. 2021 Jul 1;22(1):190. doi: 10.1186/s12931-021-01765-1.
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.
The 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% O 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.
CKMT1 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.
In summary, CKMT1 has the potential as a target for NSCLC hypoxic targeted therapy.
缺氧是实体瘤的一个突出特征。本研究旨在揭示线粒体肌酸激酶 1（CKMT1）在非小细胞肺癌（NSCLC）进展和缺氧适应中的作用。
使用 GEPIA 网站、免疫组织化学和 qRT-PCR 检测 NSCLC 组织中 CKMT1 的 mRNA 和蛋白表达。对于缺氧，将细胞暴露于 1% O 气氛中。通过 Western blot 检测 H1650 和 H1299 细胞中 CKMT1 和 HIF-1α在缺氧条件下的蛋白水平。通过 CCK8、集落形成和 Transwell 测定来测量 CKMT1 对 NSCLC 细胞增殖、侵袭和缺氧适应的作用。荧光素酶活性测定和 HIF1 特异性抑制剂（LW6）测定表明缺氧和 CKMT1 的相关功能。
CKMT1 在 NSCLC 组织中高表达，CKMT1 高水平与 NSCLC 的高病理分级显著相关。CKMT1 的敲低抑制了 H1650 和 H1299 细胞的增殖和侵袭，而缺氧可以挽救这一作用。缺氧诱导 HIF-1α和 CKMT1 在 H1650 和 H1299 细胞中的积累。此外，HIF-1 作为 CKMT1 的转录因子，在缺氧条件下可上调 CKMT1 的表达。
综上所述，CKMT1 有可能成为 NSCLC 缺氧靶向治疗的靶点。
