囊性纤维化跨膜传导调节因子通过抑制核因子κB信号通路调控宫颈癌细胞的增殖、迁移和侵袭。
CFTR Regulates the Proliferation, Migration and Invasion of Cervical Cancer Cells by Inhibiting the NF-κB Signalling Pathway.
作者信息
Wu Zhao, Li Jinke, Zhang Yi, Hu Lina, Peng Xue
机构信息
Department of Obstetrics and Gynecology, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan, People's Republic of China.
Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University; Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, Chengdu, Sichuan, People's Republic of China.
出版信息
Cancer Manag Res. 2020 Jun 18;12:4685-4697. doi: 10.2147/CMAR.S252296. eCollection 2020.
BACKGROUND
The cystic fibrosis transmembrane conductance regulator (CFTR) and nuclear factor κB (NF-κB) signalling pathways are currently regarded as co-regulators of the occurrence of cervical cancer. However, the detailed mechanism of CFTR- and NF-κB-mediated effects in cervical cancer remains to be elucidated. This study aimed to investigate the mechanism by which CFTR and NF-κB influence the development of cervical cancer.
PATIENTS AND METHODS
CFTR ΔF508 mutation and CFTR promoter methylation were detected in cervical tissue samples. NF-κB p65 and IκBα protein levels were tested in HeLa cells with CFTR overexpression and knockdown by Western blotting. The effects of CFTR on cell proliferation, migration, and invasion were examined in HeLa cells by WST-1 and soft agar assays, cell wound scratch assay, and Matrigel invasion assays, respectively. The protein-protein interaction (PPI) network was constructed by using GeneMANIA. GeneCoDis3 was used to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis on genes in the PPI network.
RESULTS
CFTR mutation and CFTR promoter methylation were not associated with the occurrence of cervical cancer. NF-κB p65 protein levels were decreased in CFTR overexpression lines and increased in CFTR knockdown lines, and IκBα levels were affected in the opposite manner, indicating that CFTR inhibited the NF-κB signalling pathway. CFTR also regulated the cell proliferation, migration, and invasion ability of cervical cancer cells. When CFTR was overexpressed, cell proliferation, migration, and invasion ability were decreased. There were 20 genes that interacted with CFTR. KEGG pathway analysis showed enrichment in the gastric acid secretion, chemokine signalling, bile secretion and apoptosis pathways.
CONCLUSION
CFTR plays an important role in cancer cell proliferation, migration and invasion by inhibiting the NF-κB signalling pathway in cervical cancer.
背景
囊性纤维化跨膜传导调节因子（CFTR）和核因子κB（NF-κB）信号通路目前被认为是宫颈癌发生的共同调节因子。然而，CFTR和NF-κB介导的宫颈癌效应的详细机制仍有待阐明。本研究旨在探讨CFTR和NF-κB影响宫颈癌发展的机制。
患者和方法
检测宫颈组织样本中的CFTR ΔF508突变和CFTR启动子甲基化。通过蛋白质免疫印迹法检测CFTR过表达和敲低的HeLa细胞中NF-κB p65和IκBα蛋白水平。分别通过WST-1和软琼脂试验、细胞划痕试验和基质胶侵袭试验检测CFTR对HeLa细胞增殖、迁移和侵袭的影响。使用GeneMANIA构建蛋白质-蛋白质相互作用（PPI）网络。使用GeneCoDis3对PPI网络中的基因进行基因本体（GO）和京都基因与基因组百科全书（KEGG）功能富集分析。
结果
CFTR突变和CFTR启动子甲基化与宫颈癌的发生无关。CFTR过表达系中NF-κB p65蛋白水平降低，CFTR敲低系中升高，IκBα水平则以相反方式受到影响，表明CFTR抑制NF-κB信号通路。CFTR还调节宫颈癌细胞的增殖、迁移和侵袭能力。当CFTR过表达时，细胞增殖、迁移和侵袭能力降低。有20个基因与CFTR相互作用。KEGG通路分析显示在胃酸分泌、趋化因子信号传导、胆汁分泌和凋亡通路中富集。
结论
CFTR通过抑制宫颈癌中的NF-κB信号通路在癌细胞增殖、迁移和侵袭中起重要作用。
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