Nanog interaction with the androgen receptor signaling axis induce ovarian cancer stem cell regulation: studies based on the CRISPR/Cas9 system.
Nanog interaction with the androgen receptor signaling axis induce ovarian cancer stem cell regulation: studies based on the CRISPR/Cas9 system.
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Nanog与雄激素受体信号轴的相互作用诱导卵巢癌干细胞调节：基于CRISPR/Cas9系统的研究
DOI：
10.1186/s13048-018-0403-2
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发表时间：
2018-05-02
影响因子：
4
通讯作者：
Liang Z
中科院分区：
文献类型：
--
作者：
Ling K;Jiang L;Liang S;Kwong J;Yang L;Li Y;PingYin;Deng Q;Liang Z
卵巢癌干细胞（OCSCs）是卵巢癌预后不良的重要因素。雄激素受体（AR）参与其他肿瘤的恶性行为已被报道。然而，AR是否与Nanog（干细胞标记物）相关并参与OCSC功能仍不清楚。在这项研究中，我们研究了Nanog与AR的相互作用，并研究了这种相互作用是否在卵巢癌细胞中诱导干细胞样特性。评估卵巢肿瘤中AR和Nanog的表达。利用CRISPR/Cas9系统构建Nanog绿色荧光蛋白（GFP）标记细胞模型，研究Nanog和AR的表达和共定位。然后，我们研究了雄激素对卵巢癌细胞系（A2780和SKOV 3）中Nanog启动子的影响。雄激素或抗雄激素治疗后，细胞增殖，迁移，球体形成，集落形成和肿瘤发生进行了评估，在体外和体内。AR和Nanog在卵巢肿瘤中均呈明显高表达。我们的结果表明Nanog表达与AR表达相关。雄激素5α-二氢睾酮（DHT）激活Nanog启动子转录。同时，经DHT处理的Nanog GFP阳性细胞表现出更高水平的增殖、迁移、球体形成和集落形成。我们还观察到Nanog GFP阳性细胞的肿瘤发生率显著高于GFP阴性细胞。Nanog GFP阳性细胞的异种移植物在体内用雄激素或抗雄激素药物处理时显示出显著差异。Nanog与AR信号轴的相互作用可能诱导或有助于OCSC调节。此外，雄激素可能通过激活Nanog启动子促进卵巢癌细胞的干性特征。这一发现值得进一步研究，因为它可能从激素的角度提供对OCSC调节的新理解，并导致对卵巢癌干细胞治疗的重新评估。本文的在线版本（10.1186/s13048-018-0403-2）包含补充材料，可供授权用户使用。
Ovarian cancer stem cells (OCSCs) contribute to the poor prognosis of ovarian cancer. Involvement of the androgen receptor (AR) in the malignant behaviors of other tumors has been reported. However, whether AR associates with Nanog (a stem cell marker) and participates in OCSC functions remain unclear. In this study, we investigated the interaction of Nanog with AR and examined whether this interaction induced stem-like properties in ovarian cancer cells. AR and Nanog expression in ovarian tumors was evaluated. Using the CRISPR/Cas9 system, we constructed a Nanog green fluorescent protein (GFP) marker cell model to investigate the expression and co-localization of Nanog and AR. Then, we examined the effect of androgen on the Nanog promoter in ovarian cancer cell lines (A2780 and SKOV3). After androgen or anti-androgen treatment, cell proliferation, migration, sphere formation, colony formation and tumorigenesis were assessed in vitro and in vivo. Both AR and Nanog expression were obviously high in ovarian tumors. Our results showed that Nanog expression was correlated with AR expression. The androgen 5α-dihydrotestosterone (DHT) activated Nanog promoter transcription. Meanwhile, Nanog GFP-positive cells treated with DHT exhibited higher levels of proliferation, migration, sphere formation and colony formation. We also observed that the tumorigenesis of Nanog GFP-positive cells was significantly higher than that of the GFP-negative cells. Xenografts of Nanog GFP-positive cells showed significant differences when treated with androgen or anti-androgen drugs in vivo. The interaction of Nanog with the AR signaling axis might induce or contribute to OCSC regulation. In addition, androgen might promote stemness characteristics in ovarian cancer cells by activating the Nanog promoter. This finding merits further study because it may provide a new understanding of OCSC regulation from a hormone perspective and lead to the reevaluation of stem cell therapy for ovarian cancer. The online version of this article (10.1186/s13048-018-0403-2) contains supplementary material, which is available to authorized users.
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影响因子：
2.9
作者：
Albini A;Bruno A;Gallo C;Pajardi G;Noonan DM;Dallaglio K
通讯作者：
Dallaglio K
影响因子：
3.3
作者：
Iwase, Haruko;Takada, Toshio;Takeshima, Nobuhiro
通讯作者：
Takeshima, Nobuhiro
影响因子：
--
作者：
Safa AR
通讯作者：
Safa AR
影响因子：
5.6
作者：
Kwon MJ;Shin YK
通讯作者：
Shin YK
雄激素/雄激素受体轴通过直接激活肝细胞癌中的nanog转录来维持和促进癌细胞干性
影响因子：
--
作者：
Jiang L;Shan J;Shen J;Wang Y;Yan P;Liu L;Zhao W;Xu Y;Zhu W;Su L;Chen J;Cheng F;Yao H;Xu H;Qian C;Liang Z
通讯作者：
Liang Z