Departments of Physiology, School of Medicine, Pusan National University, Yangsan 50612, Korea.
Obstetrics and Gynecology, School of Medicine, Pusan National University, Yangsan 50612, Korea.
BMB Rep. 2018 Oct;51(10):514-519. doi: 10.5483/BMBRep.2018.51.10.042.
Ovarian cancer is the most fatal gynecological malignancy in women and identification of new therapeutic targets is essential for the continued development of therapy for ovarian cancer. TRRAP (transformation/transcription domain-associated protein) is an adaptor protein and a component of histone acetyltransferase complex. The present study was undertaken to investigate the roles played by TRRAP in the proliferation and tumorigenicity of ovarian cancer stem cells. TRRAP expression was found to be up-regulated in the sphere cultures of A2780 ovarian cancer cells. Knockdown of TRRAP significantly decreased cell proliferation and the number of A2780 spheroids. In addition, TRRAP knockdown induced cell cycle arrest and increased apoptotic percentages of A2780 sphere cells. Notably, the mRNA levels of stemness-associated markers, that is, OCT4, SOX2, and NANOG, were suppressed in TRRAP-silenced A2780 sphere cells. In addition, TRRAP overexpression increased the mRNA level of NANOG and the transcriptional activity of NANOG promoter in these cells. Furthermore, TRRAP knockdown significantly reduced tumor growth in a murine xenograft transplantation model. Taken together, the findings of the present study suggest that TRRAP plays an important role in the regulation of the proliferation and stemness of ovarian cancer stem cells. [BMB Reports 2018; 51(10): 515-520].
卵巢癌是女性最致命的妇科恶性肿瘤，因此寻找新的治疗靶点对于卵巢癌的治疗发展至关重要。TRRAP（转化/转录结构域相关蛋白）是一种衔接蛋白，也是组蛋白乙酰转移酶复合物的一个组成部分。本研究旨在探讨 TRRAP 在卵巢癌干细胞增殖和致瘤性中的作用。研究发现，在 A2780 卵巢癌细胞的球体培养物中，TRRAP 的表达上调。TRRAP 敲低显著降低了 A2780 球体细胞的增殖和数量。此外，TRRAP 敲低诱导细胞周期停滞并增加 A2780 球体细胞的凋亡百分比。值得注意的是，在 TRRAP 沉默的 A2780 球体细胞中，与干细胞相关的标记物（即 OCT4、SOX2 和 NANOG）的 mRNA 水平受到抑制。此外，TRRAP 过表达增加了这些细胞中 NANOG 的 mRNA 水平和 NANOG 启动子的转录活性。此外，TRRAP 敲低显著降低了在小鼠异种移植移植模型中的肿瘤生长。总之，本研究的结果表明，TRRAP 在调节卵巢癌干细胞的增殖和干性方面发挥着重要作用。[BMB 报告 2018；51(10)：515-520]。
