title: Desmoglein-2 is overexpressed in non-small cell lung cancer tissues and its knockdown suppresses NSCLC growth by regulation of p27 and CDK2.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Respiratory Medicine, Jinling Hospital, Medical School of Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, Jiangsu, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Cai
authors.affiliation: Department of Respiratory Medicine, Jinling Hospital, Medical School of Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, Jiangsu, China.
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Zhu
authors.affiliation: Department of Respiratory Medicine, Jinling Hospital, Medical School of Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, Jiangsu, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Miao
authors.affiliation: Department of Respiratory Medicine, Jinling Hospital, Medical School of Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, Jiangsu, China.
authors.forename: Simei
authors.initials: S
authors.lastname: Shen
authors.affiliation: Department of Respiratory Medicine, Jinling Hospital, Medical School of Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, Jiangsu, China. suxinjs@163.com.
authors.forename: Xin
authors.initials: X
authors.lastname: Su
authors.affiliation: Department of Respiratory Medicine, Jinling Hospital, Medical School of Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, Jiangsu, China. shiyi56@126.com.
authors.forename: Yi
authors.initials: Y
authors.lastname: Shi
mesh_terms: D000072283:A549 Cells; D000328:Adult; D000368:Aged; D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D049109:Cell Proliferation; D051357:Cyclin-Dependent Kinase 2 / Q000235:genetics / Q000378:metabolism*; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics / Q000378:metabolism*; D051301:Desmoglein 2 / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008297:Male; D008819:Mice, Nude; D008875:Middle Aged; D009368:Neoplasm Transplantation; D034741:RNA, Small Interfering / Q000235:genetics; D012189:Retrospective Studies; D047368:Tumor Burden
chemical_list: C495314:DSG2 protein, human; D051301:Desmoglein 2; D034741:RNA, Small Interfering; D050760:Cyclin-Dependent Kinase Inhibitor p27; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2
keywords: Cell cycle regulation; Desmoglein-2; NSCLC; Tumor cell proliferation