Abstract
Purpose
Desmoglein-2 (Dsg2) is a cell adhesion protein of the cadherin superfamily. Altered Dsg2 expression is associated with tumorigenesis. This study determined Dsg2 expression in non-small cell lung cancer (NSCLC) tissue specimens for association with clinicopathological and survival data and then assessed the effect of Dsg2 knockdown on regulation of NSCLC cell malignant behaviors in vitro and in nude mouse xenografts.
Methods
qRT-PCR and Western blot were used to detect Dsg2 expression in 28 paired NSCLC and normal tissue samples. Immunohistochemistry was used to detect Dsg2 expression in 70 cases of paraffin-embedded NSCLC tissues. NSCLC A549, H1703, and H1299 cells were cultured with Dsg2 knockdown performed using Dsg2 siRNA. Cell viability, cell cycle, apoptosis, and colony formation were assessed. siRNA-transfected A549 cells were also used to generate tumor xenografts in nude mice.
Results
Both Dsg2 mRNA and protein were highly expressed in NSCLC tissues and associated with NSCLC size, but not with overall survival of patients. Moreover, knockdown of Dsg2 expression reduced NSCLC cell proliferation and arrested them at the G1 phase of the cell cycle, but did not significantly affect NSCLC cell apoptosis. Dsg2 knockdown downregulated cyclin-dependent kinase 2 expression and upregulated p27 expression. Nude mouse xenograft assays showed that Dsg2 knockdown inhibited NSCLC xenograft growth in vivo.
Conclusion
This study revealed the importance of Dsg2 in suppression of NSCLC development and progression. Further studies will explore whether restoration of Dsg2 expression is a novel strategy in control of NSCLC.
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Abbreviations
- AC:
-
Adenocarcinomas
- BCC:
-
Basal cell carcinomas
- Dsg:
-
Desmoglein
- NSCLC:
-
Non-small cell lung cancer
- qRT-PCR:
-
Quantitative reverse–transcription polymerase chain reaction
- SCC:
-
Squamous cell carcinomas
- siRNA:
-
Small interfering RNAs
- TNM:
-
Tumor–nodes–metastasis
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Acknowledgments
We would like to thank Dr. Zhongdong Lee of the Department of Thoracic Surgery, Jinling Hospital (Nanjing, China), for assistance in collection of tissue specimens. This study was supported in part by a Grant from the National Natural Science Foundation of China (#81470206).
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All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.
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432_2016_2250_MOESM1_ESM.tif
Database data analysis. We performed analyses of data from the online databases (the Oncomine® Platform and the Kaplan–Meier Plotter) and found that level of Dsg2 mRNA was higher in NSCLC tissues than in normal lung tissues and that level of Dsg2 mRNA associated with survival of NSCLC patients. (a) Five studies from the Oncomine® Platform showed higher level of Dsg2 expression in NSCLC tissues with more than twofold changes. (b) Kaplan–Meier Plotter. The data suggest that Dsg2 expression was associated with poor prognosis in 1926 NSCLC patients. (TIFF 577 kb)
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Cai, F., Zhu, Q., Miao, Y. et al. Desmoglein-2 is overexpressed in non-small cell lung cancer tissues and its knockdown suppresses NSCLC growth by regulation of p27 and CDK2. J Cancer Res Clin Oncol 143, 59–69 (2017). https://doi.org/10.1007/s00432-016-2250-0
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DOI: https://doi.org/10.1007/s00432-016-2250-0