Mitochondrial creatine kinase 1 in non-small cell lung cancer progression and hypoxia adaptation.
Mitochondrial creatine kinase 1 in non-small cell lung cancer progression and hypoxia adaptation.
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线粒体肌酸激酶1在非小细胞肺癌进展和低氧适应中的作用。
DOI：
10.1186/s12931-021-01765-1
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发表时间：
2021-07-01
影响因子：
5.8
通讯作者：
Lv Y
中科院分区：
文献类型：
--
作者：
Li M;Liu H;Li J;Guo S;Lv Y
缺氧是实体癌的一个显著特征。本研究旨在揭示线粒体肌酸激酶1(CKMT1)在非小细胞肺癌(NSCLC)进展和低氧适应中的作用。采用GEPIA网络、免疫组织化学和定量逆转录聚合酶链式反应技术检测非小细胞肺癌组织中CKMT1mRNA和蛋白的表达。对于低氧，细胞暴露在1%O2气氛中。免疫印迹法检测缺氧对H1650和H1299细胞HIF1、α和CKMT1蛋白表达的影响。通过CCK8、集落形成和Transwell实验检测CKMT1在NSCLC细胞增殖、侵袭和低氧适应中的作用。荧光素酶活性检测和HIF1特异性抑制物(LW6)检测表明低氧与CKMT1的相关功能。CKMT1在NSCLC组织中高表达，且CKMT1的高表达水平与NSCLC的病理分级密切相关。CKMT1基因敲除可抑制H1650和H1299细胞的增殖和侵袭，低氧可使其恢复。低氧可诱导H1650和H1299细胞缺氧诱导因子-1α积聚和CKMT1表达。此外，HIF-1作为CKMT1的转录因子，在低氧条件下可上调CKMT1的表达。总之，CKMT1有可能成为非小细胞肺癌缺氧靶向治疗的靶点。
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% 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. 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.
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GEPIA：用于癌症和正常基因表达谱和交互式分析的网络服务器。
影响因子：
14.9
作者：
Tang Z;Li C;Kang B;Gao G;Li C;Zhang Z
通讯作者：
Zhang Z
影响因子：
13.8
作者：
Semenza GL
通讯作者：
Semenza GL
影响因子：
8.8
作者：
通讯作者：
--
影响因子：
3.9
作者：
Amamoto, Rie;Uchiumi, Takeshi;Kang, Dongchon
通讯作者：
Kang, Dongchon
DOI：
10.1007/978-981-10-3233-2_27
发表时间：
2017-01-01
期刊：
RUNX PROTEINS IN DEVELOPMENT AND CANCER
影响因子：
--
作者：
Lee, Sun Hee;Manandhar, Sarala;Lee, You Mie
通讯作者：
Lee, You Mie