Yin Yang-1 suppresses pancreatic ductal adenocarcinoma cell proliferation and tumor growth by regulating SOX2OT-SOX2 axis.
Yin Yang-1 suppresses pancreatic ductal adenocarcinoma cell proliferation and tumor growth by regulating SOX2OT-SOX2 axis.
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DOI：
10.1016/j.canlet.2017.08.032
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发表时间：
2017-11
期刊：
影响因子：
9.7
通讯作者：
Jing-Jing Zhang-Jing;Yi Zhu;Xiongfei Zhang;Dong Liu;Yan Wang;Chuang Yang;Guo-dong Shi;Yunpeng Peng
中科院分区：
文献类型：
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作者：
Jing-Jing Zhang-Jing;Yi Zhu;Xiongfei Zhang;Dong Liu;Yan Wang;Chuang Yang;Guo-dong Shi;Yunpeng Peng
转录调节因子Yin Yang-1（YY 1）在胰腺导管腺癌（PDAC）中起肿瘤抑制作用。然而，YY 1在PDAC细胞增殖中的功能仍有待阐明。在本研究中，我们发现YY 1的过表达抑制PDAC细胞的增殖，并降低长链非编码RNA（lncRNA）SOX 2 OT及其潜在靶基因SOX 2的表达。荧光素酶报告，电泳迁移率变动（EMSA）和染色质免疫沉淀（ChIP）试验显示结合YY 1的SOX 2 OT启动子。此外，YY 1通过抑制SOX 2 OT转录和随后降低SOX 2表达来抑制PDAC细胞增殖。此外，YY 1表达与PDAC组织中的SOX 2 OT和SOX 2表达呈统计学负相关，SOX 2 OT的低水平表达预示PDAC患者的预后更好。这些结果证实了YY 1对PDAC细胞的抗增殖作用，这与SOX 2 OT依赖性机制中的SOX 2下调有关。虽然其他未被发现的机制可能参与YY 1介导的肿瘤抑制作用，本研究表明，SOX 2 OT可能作为PDAC的肿瘤促进剂，并可能代表一个有价值的诊断和治疗靶点。
The transcription regulator Yin Yang-1 (YY1) serves as a tumor suppressor in pancreatic ductal adenocarcinoma (PDAC). However, the function of YY1 in proliferation of PDAC cells remains to be clarified. In this study, we found that overexpression of YY1 suppressed proliferation and decreased the expression of long non-coding RNA (lncRNA) SOX2OT and its potential target gene SOX2 in PDAC cells. Luciferase reporter, electrophoretic mobility shift (EMSA), and chromatin immunoprecipitation (ChIP) assays revealed binding of YY1 to the SOX2OT promoter. Moreover, YY1 suppressed PDAC cell proliferation through SOX2OT transcriptional inhibition and subsequent decreased SOX2 expression. In addition, YY1 expression was statistically negatively correlated with SOX2OT and SOX2 expression in PDAC tissues and lower level expression of SOX2OT predicted better outcome in PDAC patients. These results confirmed the anti-proliferation effect of YY1 on PDAC cells, which was associated with SOX2 down-regulation in a SOX2OT-dependent mechanism. Although other undiscovered mechanisms may be involved in the YY1-mediated tumor suppression role, the present study suggests that SOX2OT may act as a tumor promotor in PDAC and may represent a valuable diagnostic and therapeutic target.