Sex-Determining Region Y-box 2 Promotes Growth of Lung Squamous Cell Carcinoma and Directly Targets Cyclin D1.
Sex-determining region Y-box 2 (SOX2) is an oncogene known to be amplified and overexpressed in various human malignancies, including lung squamous cell carcinoma (SCC). However, the role played by SOX2 in lung SCC development remains to be elucidated. We measured the levels of SOX2 and cyclin D1 mRNA and protein expression in lung SCC tissues and a lung SCC cell line, and found that both levels were dramatically upregulated in specimens of lung SCC tissue when compared with their expression levels in samples of adjacent nonneoplastic tissue. The lung SCC cell line also showed higher levels of SOX2 and cyclin D1 expression than a normal human bronchial epithelium cell line. After using RNA interference to knock down SOX2 expression in NCI-H520 lung SCC cells, their proliferation was reduced. Furthermore, overexpression of SOX2 promoted the proliferation of normal human bronchial epithelium cells. To further determine whether cyclin D1 was downstream target gene of SOX2, we measured the levels of cyclin D1 expression that occurred when SOX2 was knocked down or overexpressed. SOX2 knockdown significantly decreased the levels of cyclin D1 mRNA and protein expression, while SOX2 overexpression upregulated the levels of cyclin D1. We used bioinformatics data to identify potential cyclin D1 promoter binding sites for SOX2. Results of luciferase reporter assays, electrophoretic mobility shift assays, and chromatin immunoprecipitation assays confirmed that cyclin D1 was a direct target of transcription factor SOX2 in human lung SCC cells.
1 Department of Respiration, Chenzhou First People's Hospital , Chenzhou, China .
Chiguan
C
Li
1 Department of Respiration, Chenzhou First People's Hospital , Chenzhou, China .
Bingwen
B
He
1 Department of Respiration, Chenzhou First People's Hospital , Chenzhou, China .
Cuiping
C
Huang
2 Department of Respiration, Xiangya Hospital, Central South University , Changsha, China .
Huaping
H
Yang
2 Department of Respiration, Xiangya Hospital, Central South University , Changsha, China .
Liming
L
Cao
3 State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Disease, Department of Thoracic Surgery of the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China .
Jun
J
Huang
2 Department of Respiration, Xiangya Hospital, Central South University , Changsha, China .
Chengping
C
Hu
D001980:Bronchi / Q000166:cytology; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000235:genetics*; D004847:Epithelial Cells / Q000166:cytology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism* / Q000502:physiology
C530104:CCND1 protein, human; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; D019938:Cyclin D1
SOX2; cyclin D1; lung squamous cell carcinoma; proliferation