title: SOX2 suppresses CDKN1A to sustain growth of lung squamous cell carcinoma.
abstract: Since the SOX2 amplification was identified in lung squamous cell carcinoma (lung SCC), SOX2 transcriptional downstream targets have been actively investigated; however, such targets are often cell line specific. Here, in order to identify highly consensus SOX2 downstream genes in lung SCC cells, we used RNA-seq data from 178 lung SCC specimens (containing tumor and tumor-associated cells) and analyzed the correlation between SOX2 and previously-reported SOX2-controlled genes in lung SCC. In addition, we used another RNA-seq dataset from 105 non-small cell lung cancer cell lines (NSCLC; including 4 lung SCC cell lines) and again analyzed the correlation between SOX2 and the reported SOX2-controlled genes in the NSCLC cell lines (no tumor-associated cells). We combined the two analyses and identified genes commonly correlated with SOX2 in both datasets. Among the 99 genes reported as SOX2 downstream and/or correlated genes, we found 4 negatively-correlated (e.g., CDKN1A) and 11 positively-correlated genes with SOX2. We used biological studies to demonstrate that CDKN1A was suppressed by SOX2 in lung SCC cells. G1 cell cycle arrest induced by SOX2 siRNA was rescued by CDKN1A siRNA. These results indicate that the tumorigenic effect of SOX2 in lung SCC cells is mediated in part by suppression of CDKN1A.
authors: Department of General Surgery,Okayama, Japan, 700-8505.
authors: Takuya
authors: T
authors: Fukazawa
authors: Department of Electrical Engineering and Computing Systems, University of Cincinnati, Cincinnati, Ohio, 45221.|Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, 45229-3039.
authors: Minzhe
authors: M
authors: Guo
authors: Department of General Surgery,Okayama, Japan, 700-8505.
authors: Naomasa
authors: N
authors: Ishida
authors: Department of General Surgery,Okayama, Japan, 700-8505.
authors: Tomoki
authors: T
authors: Yamatsuji
authors: Department of General Surgery,Okayama, Japan, 700-8505.
authors: Munenori
authors: M
authors: Takaoka
authors: Department of General Surgery,Okayama, Japan, 700-8505.
authors: Etsuko
authors: E
authors: Yokota
authors: Department of General Surgery,Okayama, Japan, 700-8505.
authors: Minoru
authors: M
authors: Haisa
authors: Kawasaki Hospital Research Unit, Kawasaki Medical School, Okayama, Japan, 700-8505.
authors: Noriko
authors: N
authors: Miyake
authors: Kawasaki Hospital Research Unit, Kawasaki Medical School, Okayama, Japan, 700-8505.
authors: Tomoko
authors: T
authors: Ikeda
authors: Division of Hematology and Oncology, Indiana University School of Medicine, Indianapolis, Indiana, 46202.
authors: Tatsuo
authors: T
authors: Okui
authors: Department of General Internal Medicine 4,Okayama, Japan, 700-8505.
authors: Nagio
authors: N
authors: Takigawa
authors: Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, 45229-3039.
authors: Yutaka
authors: Y
authors: Maeda
authors: Department of General Surgery,Okayama, Japan, 700-8505.
authors: Yoshio
authors: Y
authors: Naomoto
mesh_terms: D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D059585:G1 Phase Cell Cycle Checkpoints; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D055748:SOXB1 Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D017423:Sequence Analysis, RNA; D014183:Transplantation, Heterologous
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D055748:SOXB1 Transcription Factors