Upregulation of SOX4 antagonizes cellular senescence in esophageal squamous cell carcinoma.
Upregulation of SOX4 antagonizes cellular senescence in esophageal squamous cell carcinoma.
复制标题
SOX4 的上调可拮抗食管鳞状细胞癌中的细胞衰老
DOI：
10.3892/ol.2016.4799
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发表时间：
2016-08
期刊：
影响因子：
2.9
通讯作者：
Yang W
中科院分区：
文献类型：
--
作者：
Han R;Huang S;Bao Y;Liu X;Peng X;Chen Z;Wang Q;Wang J;Zhang Q;Wang T;Zheng D;Yang W
衰老是由多种细胞应激（如端粒侵蚀、DNA损伤和致癌信号传导）引起的终末细胞增殖停滞，被经典地认为是肿瘤防御屏障。然而，癌细胞克服衰老的机制尚未确定。在这项研究中，食管鳞状细胞癌（ESCC）的基因表达阵列数据与配对的正常组织进行了比较，并显示了一组基因，包括蛋白酶，趋化因子和炎症因子，在ESCC中上调，表现出衰老相关的分泌表型。此外，逆转录-定量聚合酶链反应被用来证明性别决定区Y-box 4（SOX 4）在ESCC中上调，其表达与衰老标志物呈负相关。此外，通过短发夹RNA敲低SOX 4表达降低了ESCC细胞增殖并增强了阿霉素诱导的细胞衰老。这些结果揭示了ESCC中衰老微环境的存在，并表明SOX 4在ESCC进展中具有重要的抗衰老作用。
Senescence, a terminal cell proliferation arrest that is caused by a variety of cellular stresses such as telomere erosion, DNA damage and oncogenic signaling, is classically considered a tumor defense barrier. However, the mechanism by which cancer cells overcome senescence is undetermined. In this study, the gene expression array data of esophageal squamous cell carcinoma (ESCC) was compared with paired normal tissues and showed that a cohort of genes, including proteinases, chemokines and inflammation factors, are upregulated in ESCC, which exhibits the senescence-associated secretory phenotype. In addition, reverse transcription-quantitative polymerase chain reaction was used to demonstrate that gender determining region Y-box 4 (SOX4) is upregulated in ESCC, and that its expression is inversely correlated with senescence markers. In addition, the knockdown of SOX4 expression by short hairpin RNA decreases ESCC cell proliferation and enhances doxorubicin-induced cell senescence. These results reveal the presence of a senescent microenvironment in ESCC, and suggest an important antisenescence role of SOX4 in ESCC progression.