SOX9, a potential tumor suppressor in cervical cancer, transactivates p21WAF1/CIP1 and suppresses cervical tumor growth.
SOX9, a potential tumor suppressor in cervical cancer, transactivates p21WAF1/CIP1 and suppresses cervical tumor growth.
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SOX9 是宫颈癌中的一种潜在肿瘤抑制因子，可反式激活 p21WAF1/CIP1 并抑制宫颈肿瘤生长。
DOI：
10.18632/oncotarget.4133
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发表时间：
2015-08-21
期刊：
影响因子：
--
通讯作者：
Zheng PS
中科院分区：
文献类型：
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作者：
Wang HY;Lian P;Zheng PS
性别决定区Y-box 9蛋白(SOX9)是一种转录因子，可作为癌基因和肿瘤抑制因子，其作用取决于肿瘤的来源。我们发现，与正常宫颈组织相比，宫颈原位癌尤其是浸润性宫颈癌中SOX9的表达呈进行性降低。通过沉默和过表达SOX9来评价SOX9对宫颈癌细胞增殖、存活和肿瘤形成的影响。SOX9在宫颈癌细胞(SiHA和C33A)中的过表达抑制了细胞的体外生长和体内肿瘤的形成。一致认为，SOX9在HeLa细胞中的沉默促进了培养中的细胞生长和小鼠肿瘤的形成。SOX9通过特定的启动子区域反式激活p21WAF1/CIP1，从而阻断G1/S的转变。染色质定量免疫沉淀分析表明SOX9与p21WAF1/CIP1启动子的特定区域之间存在物理相互作用。我们认为SOX9是一个潜在的治疗宫颈癌的靶点，它可以特异性地反式激活p21WAF1/CIP1。
Sex-determining region Y-box 9 protein (SOX9) is a transcription factor that may act as both oncogene and tumor suppressor depending on tumor origin. Here we found that SOX9 expression was progressively decreased in cervical carcinoma in situ and especially in invasive cervical carcinoma, compared with normal cervix tissue. The effects of SOX9 on the proliferation, viability, and tumor formation of cervical carcinoma cells were assessed through the silencing and overexpression of SOX9. Overexpression of SOX9 in cervical carcinoma cells (SiHa and C33A) inhibited cell growth in vitro and tumor formation in vivo. In agreement, the silencing of SOX9 in HeLa cells promoted cell growth in culture and tumor formation in mice. Overexpression of SOX9 transactivated p21WAF1/CIP1 via a specific promoter region, thus blocking G1/S transition. The quantitative chromatin immunoprecipitation analysis revealed physical interaction between SOX9 and the specific region of the p21WAF1/CIP1 promoter. We suggest that SOX9 is a potential therapeutic target in cervical carcinoma, that specifically transactivates p21WAF1/CIP1.