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. 2018;18(2):109-115.
doi: 10.2174/1566524018666180705113642.

ZNF424 Induces Apoptosis and Inhibits Proliferation in Lung Carcinoma Cells

W Liu  1 , W Yuan  1 , X Li  2 , J Zhuang  3 , X Mo  1 , G Dai  1 , Y Wang  1 , J Chen  3 , Y Wan  1 , Y Li  1 , X Zhu  3 , Y Chen  1 , S Luo  1 , Z Jiang  1 , Y Shi  1 , F Chen  1 , L Cao  1 , X Ye  1 , X Fan  1 , P Zhu  3 , K Zhang  4 , X Wu  1
Affiliations

ZNF424 Induces Apoptosis and Inhibits Proliferation in Lung Carcinoma Cells

W Liu et al. Curr Mol Med. 2018.

Abstract

Background: Previously, we showed that the Zinc finger-containing transcription factor ZNF424 inhibits p21 transcription, which has been widely associated with various cancers. However, because the roles of ZNF424 in tumorigenesis have not been characterized, we correlated ZNF424 expression with tumorigenesis in lung cancer.

Results: The present immunohistochemical analyses show significantly lower ZNF424 expression levels in 43 of 60 lung cancer tissues compared with adjacent tissues. Moreover, flow cytometry assays indicated that overexpression of ZNF424 induces apoptosis in A549 human lung carcinoma cells, and overexpression of ZNF424 significantly increases numbers of G1 phase cells and decreases numbers of S phase cells, suggesting that ZNF424 inhibits proliferation. Western Blot analyses show that overexpression of ZNF424 decreases protein expression levels of the mitogen-activated protein kinase (MAPK) signaling proteins P-P38 and P-ERK in A549 cells.

Conclusion: These are the first data to associate ZNF424 with tumorigenesis and demonstrate an inhibitory role in lung cancer, indicating the potential of ZNF424 expression as a diagnostic marker of lung tumorigenesis.

Keywords: MAPK pathway; ZNF424; apoptosis; lung cancer..

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Figures

Fig. (1)
Fig. (1)
ZNF424 is upregulated in lung cancers. (a) Immunohistochemistry (IHC) analyses of 60 lung carcinoma samples from the Hunan Cancer Hospital; (b) Quantitative analysis, P < 0.01.
Fig. (2)
Fig. (2)
Overexpression of ZNF424 induces apoptosis in A549 cells. (a) Apoptotic A549 cells were counted using flow cytometry after transfection with ZNF424 overexpression plasmid and empty vehicle; (b) Quantitative analysis of flow cytometry data; (c) Western blot analysis of cleaved caspase 3 in ZNF424 overexpressing A549 cells; (d) Protein expression levels were quantified and analyzed using ImageJ and GraphPad software, respectively.
Fig. (3)
Fig. (3)
Ectopic expression of ZNF424 induces G1/S arrest in A549 cells by regulating cyclin proteins and cyclin-dependent kinase. (a, b) Cell cycle stages were determined using flow cytometry; (c) Quantitative analysis; (d-f) Western blotting analyses of cell cycle-related proteins are presented with quantitative densitometric analyses.
Fig. (4)
Fig. (4)
ZNF424 overexpression inhibits proliferation through the P38/ERK MAPK pathway. (a) Western blots of MAPK protein; (b) Quantitative densitometric analysis.
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References

    1. Bellefroid E.J., Poncelet D.A., Lecocq P.J., Revelant O., Martial J.A. The evolutionarily conserved Kruppel-associated box domain defines a subfamily of eukaryotic multifingered proteins. Proc. Natl. Acad. Sci. USA. 1991;88(9):3608–3612. - PMC - PubMed
    1. Thomas J.H., Emerson R.O. Evolution of C2H2-zinc finger genes revisited. BMC Evol. Biol. 2009;9:51. - PMC - PubMed
    1. Huntley S., Baggott D.M., Hamilton A.T., et al. A comprehensive catalog of human KRAB-associated zinc finger genes: insights into the evolutionary history of a large family of transcriptional repressors. Genome Res. 2006;16(5):669–677. - PMC - PubMed
    1. Gonzalez-Lamuno D., Loukili N., Garcia-Fuentes M., Thomson T.M. Expression and regulation of the transcriptional repressor ZNF43 in Ewing sarcoma cells. Pediatr. Pathol. Mol. Med. 2002;21(6):531–540. - PubMed
    1. Huang C., Jia Y., Yang S., et al. Characterization of ZNF23, a KRAB-containing protein that is downregulated in human cancers and inhibits cell cycle progression. Exp. Cell Res. 2007;313(2):254–263. - PubMed

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