白细胞介素-33通过调控miR-128-3p/CDIP1信号通路促进非小细胞肺癌细胞生长。
IL-33 Promotes the Growth of Non-Small Cell Lung Cancer Cells Through Regulating miR-128-3p/CDIP1 Signalling Pathway.
作者信息
Zhou Xiaorong, Feng Yuxu, Liu Siwen, Li Chenchen, Teng Yue, Li Xiaoyou, Lu Jianwei
机构信息
Department of Medical Oncology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, 210009 Jiangsu Province, People's Republic of China.
Department of Orthopedics, The Pukou Centre Hospital, Nanjing, 210009 Jiangsu Province, People's Republic of China.
出版信息
Cancer Manag Res. 2021 Mar 12;13:2379-2388. doi: 10.2147/CMAR.S276297. eCollection 2021.
BACKGROUND
Non-small cell lung cancer (NSCLC) is one of the leading causes of cancer-related deaths, and it is also the most frequently diagnosed cancer. Previous studies indicate that IL-33 plays a crucial role in the development of NSCLC. In recent years, the role of miRNAs in cancer has become increasingly clear. However, reports focused on the relation between IL-33 and miRNAs in NSCLC have been limited.
METHODS
The expression of IL-33 and miR-128-3p was detected by qPCR. MTT, EdU, and colony formation assays were used to detect the proliferation ability of NSCLC cells. Transwell assay was used to investigate the migration and invasion of NSCLC cells. The expression of bax, cyt-c, and caspase 3 was detected by Western blot. Finally, in vivo tumor xenograft was used to detect the effects of IL-33 and miR-128-3p on tumor growth capacity.
RESULTS
IL-33 was notably increased in the serum and tumor tissue of NSCLC patients. The in vitro function study revealed that IL-33 significantly promotes the proliferation, migration, and invasion of the NSCLC cells. In vivo experiments further confirmed the pro-tumor effect of IL-33 on NSCLC. The study on the underlying mechanism elucidated that IL-33 regulates the expression of miR-128-3p, which can directly target and inhibit the expression of CDIP1. Furthermore, IL-33 regulates the expression of downstream apoptotic proteins such as bax, cyt-c, and caspase3. Rescue experiments demonstrated that miR-28-3p can reverse the effect of IL-33.
CONCLUSION
These findings indicated that IL-33 and miR-128-3p may play a potential role in the diagnosis and treatment of NSCLC.
背景
非小细胞肺癌（NSCLC）是癌症相关死亡的主要原因之一，也是最常被诊断出的癌症。先前的研究表明，IL-33在NSCLC的发展中起关键作用。近年来，miRNA在癌症中的作用越来越清晰。然而，关于NSCLC中IL-33与miRNA之间关系的报道有限。
方法
通过qPCR检测IL-33和miR-128-3p的表达。采用MTT、EdU和集落形成试验检测NSCLC细胞的增殖能力。用Transwell试验研究NSCLC细胞的迁移和侵袭。通过蛋白质印迹法检测bax、cyt-c和caspase 3的表达。最后，采用体内肿瘤异种移植检测IL-33和miR-128-3p对肿瘤生长能力的影响。
结果
NSCLC患者血清和肿瘤组织中IL-33显著升高。体外功能研究表明，IL-33显著促进NSCLC细胞的增殖、迁移和侵袭。体内实验进一步证实了IL-33对NSCLC的促肿瘤作用。对潜在机制的研究表明，IL-33调节miR-128-3p的表达，miR-128-3p可直接靶向并抑制CDIP1的表达。此外，IL-33调节下游凋亡蛋白如bax、cyt-c和caspase3的表达。挽救实验表明，miR-28-3p可逆转IL-33的作用。
结论
这些发现表明，IL-33和miR-128-3p可能在NSCLC的诊断和治疗中发挥潜在作用。
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