Zhu Hailing, Lu Quan, Lu Qing, Shen Xuemin, Yu Liuyang
Department of Emergency, Jingmen No. 1 People's Hospital, Jingmen, Hubei, People's Republic of China.
Department of Neurology, Jingmen No. 1 People's Hospital, Jingmen, Hubei, People's Republic of China.
Cancer Manag Res. 2021 Apr 19;13:3429-3442. doi: 10.2147/CMAR.S290966. eCollection 2021.
Non-small cell lung carcinoma (NSCLC) is the major histological subtype of cancer cases. In the present study, we investigated the association between Matrine, an active component of Chinese medicine, and circFUT8 in NSCLC cells.
The proliferation ability of NSCLC cells was assessed by MTT and colony-forming assays. Flow cytometry assay was performed to show the apoptosis and cell cycle distribution in NSCLC cells. The protein expression levels of Bcl-2, Cleaved Caspase-3 (C-Caspase3), and YES proto-oncogene 1 (YES1) were measured by Western blot assay. Migration and invasion of NSCLC cells were determined by transwell assay. The expression levels of circFUT8, miR-944 and YES1 were quantified by real-time quantitative polymerase chain reaction (RT-qPCR) assay. The interaction relationship between miR-944 and circFUT8 or YES1 was confirmed by dual-luciferase reporter assay. The anti-tumor role of Matrine in vivo was explored by a xenograft experiment.
Matrine functioned as a carcinoma inhibitor by repressing proliferation, cell cycle process, migration, and invasion while inducing apoptosis in NSCLC cells. Importantly, overexpression of circFUT8 counteracted Matrine-induced effects on NSCLC cells. MiR-944, interacted with YES1, was a target of circFUT8. Under Matrine condition, overexpression of circFUT8 increased proliferation, migration, and invasion while inhibited apoptosis, which was abolished by the upregulation of miR-944. Whereas the silencing of YES1 counteracted miR-944 inhibitor-induced effects on NSCLC cells. Eventually, we also confirmed that Matrine impeded NSCLC tumor growth in vivo.
Matrine regulated proliferation, apoptosis, cell cycle, migration, and invasion of NSCLC cells through the circFUT8/miR-944/YES1 axis, which provided novel information for Matrine in NSCLC.
非小细胞肺癌（NSCLC）是癌症病例的主要组织学亚型。在本研究中，我们调查了中药活性成分苦参碱与NSCLC细胞中circFUT8之间的关联。
通过MTT和集落形成试验评估NSCLC细胞的增殖能力。进行流式细胞术检测以显示NSCLC细胞中的凋亡和细胞周期分布。通过蛋白质免疫印迹法检测Bcl-2、裂解的半胱天冬酶-3（C-Caspase3）和原癌基因1（YES1）的蛋白表达水平。通过Transwell试验测定NSCLC细胞的迁移和侵袭能力。通过实时定量聚合酶链反应（RT-qPCR）检测circFUT8、miR-944和YES1的表达水平。通过双荧光素酶报告基因试验证实miR-944与circFUT8或YES1之间的相互作用关系。通过异种移植实验探索苦参碱在体内的抗肿瘤作用。
苦参碱通过抑制NSCLC细胞的增殖、细胞周期进程、迁移和侵袭，同时诱导细胞凋亡，发挥癌抑制剂的作用。重要的是，circFUT8的过表达抵消了苦参碱对NSCLC细胞的诱导作用。与YES1相互作用的miR-944是circFUT8的靶标。在苦参碱条件下，circFUT8的过表达增加了增殖、迁移和侵袭，同时抑制了细胞凋亡，而miR-944的上调消除了这种作用。而YES1的沉默抵消了miR-944抑制剂对NSCLC细胞诱导的作用。最终，我们还证实了苦参碱在体内可抑制NSCLC肿瘤生长。
苦参碱通过circFUT8/miR-944/YES1轴调节NSCLC细胞的增殖、凋亡、细胞周期、迁移和侵袭，这为苦参碱在NSCLC中的应用提供了新的信息。
