CFTR Regulates the Proliferation, Migration and Invasion of Cervical Cancer Cells by Inhibiting the NF-κB Signalling Pathway

Overview

Journal Cancer Manag Res

Publisher Dove Medical Press

Specialty Oncology

Date 2020 Jul 2

PMID 32606960

Citations 8

Authors

Zhao Wu

Jinke Li

Yi Zhang

Lina Hu

Xue Peng

Affiliations

Soon will be listed here.

Abstract

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.

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References

Ali A, Kim S, Kim M, Choi M, Kang S, Cho G . O-GlcNAcylation of NF-κB Promotes Lung Metastasis of Cervical Cancer Cells via Upregulation of CXCR4 Expression. Mol Cells. 2017; 40(7):476-484. PMC: 5547217. DOI: 10.14348/molcells.2017.2309. View

Vidal E, Sayols S, Moran S, Guillaumet-Adkins A, Schroeder M, Royo R . A DNA methylation map of human cancer at single base-pair resolution. Oncogene. 2017; 36(40):5648-5657. PMC: 5633654. DOI: 10.1038/onc.2017.176. View

Castle P, Rodriguez A, Burk R, Herrero R, Wacholder S, Alfaro M . Short term persistence of human papillomavirus and risk of cervical precancer and cancer: population based cohort study. BMJ. 2009; 339:b2569. PMC: 2718087. DOI: 10.1136/bmj.b2569. View

Iliopoulos D, Hirsch H, Struhl K . An epigenetic switch involving NF-kappaB, Lin28, Let-7 MicroRNA, and IL6 links inflammation to cell transformation. Cell. 2009; 139(4):693-706. PMC: 2783826. DOI: 10.1016/j.cell.2009.10.014. View

Yang A, Sun Y, Mao C, Yang S, Huang M, Deng M . Folate Protects Hepatocytes of Hyperhomocysteinemia Mice From Apoptosis via Cystic Fibrosis Transmembrane Conductance Regulator (CFTR)-Activated Endoplasmic Reticulum Stress. J Cell Biochem. 2017; 118(9):2921-2932. DOI: 10.1002/jcb.25946. View

Li Y, Sun Z, Wu Y, Babovic-Vuksanovic D, Li Y, Cunningham J . Cystic fibrosis transmembrane conductance regulator gene mutation and lung cancer risk. Lung Cancer. 2010; 70(1):14-21. PMC: 2895007. DOI: 10.1016/j.lungcan.2010.01.005. View

Truninger K, Malik N, Ammann R, Muellhaupt B, Seifert B, Muller H . Mutations of the cystic fibrosis gene in patients with chronic pancreatitis. Am J Gastroenterol. 2001; 96(9):2657-61. DOI: 10.1111/j.1572-0241.2001.04047.x. View

Wu Z, Peng X, Li J, Zhang Y, Hu L . Constitutive activation of nuclear factor κB contributes to cystic fibrosis transmembrane conductance regulator expression and promotes human cervical cancer progression and poor prognosis. Int J Gynecol Cancer. 2013; 23(5):906-15. DOI: 10.1097/IGC.0b013e318292da82. View

Moran O . The gating of the CFTR channel. Cell Mol Life Sci. 2016; 74(1):85-92. PMC: 11107742. DOI: 10.1007/s00018-016-2390-z. View

10.

Peng X, Wu Z, Yu L, Li J, Xu W, Chan H . Overexpression of cystic fibrosis transmembrane conductance regulator (CFTR) is associated with human cervical cancer malignancy, progression and prognosis. Gynecol Oncol. 2012; 125(2):470-6. DOI: 10.1016/j.ygyno.2012.02.015. View

11.

Bray F, Ferlay J, Soerjomataram I, Siegel R, Torre L, Jemal A . Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018; 68(6):394-424. DOI: 10.3322/caac.21492. View

12.

Fusella F, Secli L, Busso E, Krepelova A, Moiso E, Rocca S . The IKK/NF-κB signaling pathway requires Morgana to drive breast cancer metastasis. Nat Commun. 2017; 8(1):1636. PMC: 5696377. DOI: 10.1038/s41467-017-01829-1. View

13.

Ren Z, Wang L, Cui J, Huoc Z, Xue J, Cui H . Resveratrol inhibits NF-kB signaling through suppression of p65 and IkappaB kinase activities. Pharmazie. 2013; 68(8):689-94. View

14.

Murdoch C, Finn A . Chemokine receptors and their role in inflammation and infectious diseases. Blood. 2000; 95(10):3032-43. View

15.

Wine J, Dean M, Glavac D . Natural animal models of human genetic diseases. Methods Mol Med. 2002; 70:31-46. DOI: 10.1385/1-59259-187-6:31. View

16.

Saslow D, Solomon D, Lawson H, Killackey M, Kulasingam S, Cain J . American Cancer Society, American Society for Colposcopy and Cervical Pathology, and American Society for Clinical Pathology screening guidelines for the prevention and early detection of cervical cancer. CA Cancer J Clin. 2012; 62(3):147-72. PMC: 3801360. DOI: 10.3322/caac.21139. View

17.

Zhang Y, Huo F, Wei L, Gong C, Pan Y, Mou J . PAK5-mediated phosphorylation and nuclear translocation of NF-κB-p65 promotes breast cancer cell proliferation in vitro and in vivo. J Exp Clin Cancer Res. 2017; 36(1):146. PMC: 5645986. DOI: 10.1186/s13046-017-0610-5. View

18.

Girardet A, Viart V, Plaza S, Daina G, De Rycke M, des Georges M . The improvement of the best practice guidelines for preimplantation genetic diagnosis of cystic fibrosis: toward an international consensus. Eur J Hum Genet. 2015; 24(4):469-78. PMC: 4929885. DOI: 10.1038/ejhg.2015.99. View

19.

Perkins N . The diverse and complex roles of NF-κB subunits in cancer. Nat Rev Cancer. 2012; 12(2):121-32. DOI: 10.1038/nrc3204. View

20.

Yuan P, He X, Rong Y, Cao J, Li Y, Hu Y . KRAS/NF-κB/YY1/miR-489 Signaling Axis Controls Pancreatic Cancer Metastasis. Cancer Res. 2016; 77(1):100-111. DOI: 10.1158/0008-5472.CAN-16-1898. View