SOX2 suppresses CDKN1A to sustain growth of lung squamous cell carcinoma.
SOX2 suppresses CDKN1A to sustain growth of lung squamous cell carcinoma.
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DOI：
10.1038/srep20113
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发表时间：
2016-02-05
影响因子：
4.6
通讯作者：
Naomoto Y
中科院分区：
文献类型：
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作者：
Fukazawa T;Guo M;Ishida N;Yamatsuji T;Takaoka M;Yokota E;Haisa M;Miyake N;Ikeda T;Okui T;Takigawa N;Maeda Y;Naomoto Y
自从在肺鳞状细胞癌（肺SCC）中鉴定出S 0X 2扩增以来，S 0X 2转录下游靶标已被积极研究;然而，此类靶标通常是细胞系特异性的。在这里，为了鉴定肺SCC细胞中高度一致的SOX 2下游基因，我们使用了来自178个肺SCC标本（包含肿瘤和肿瘤相关细胞）的RNA-seq数据，并分析了SOX 2与先前报道的肺SCC中SOX 2控制基因之间的相关性。此外，我们使用了来自105个非小细胞肺癌细胞系（NSCLC;包括4个肺SCC细胞系）的另一个RNA-seq数据集，并再次分析了SOX 2与NSCLC细胞系（无肿瘤相关细胞）中报告的SOX 2控制基因之间的相关性。我们结合了这两种分析，并在两个数据集中鉴定了通常与SOX 2相关的基因。在报道为SOX 2下游和/或相关基因的99个基因中，我们发现4个负相关（例如，CDKN 1A）和11个与SOX 2正相关的基因。我们使用生物学研究来证明CDKN 1A在肺SCC细胞中被SOX 2抑制。CDKN 1A siRNA可挽救SOX 2 siRNA诱导的G1期细胞阻滞。这些结果表明，SOX 2在肺SCC细胞中的致瘤作用部分是通过抑制CDKN 1A介导的。
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.