Epigenetic repression of PDZ-LIM domain-containing protein 2 promotes ovarian cancer via NOS2-derived nitric oxide signaling.
Epigenetic repression of PDZ-LIM domain-containing protein 2 promotes ovarian cancer via NOS2-derived nitric oxide signaling.
复制标题
含 PDZ-LIM 结构域的蛋白 2 的表观遗传抑制通过 NOS2 衍生的一氧化氮信号传导促进卵巢癌
DOI：
10.18632/oncotarget.6368
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发表时间：
2016-01-12
期刊：
影响因子：
--
通讯作者：
Wei Y
中科院分区：
文献类型：
--
作者：
Zhao L;Yu C;Zhou S;Lau WB;Lau B;Luo Z;Lin Q;Yang H;Xuan Y;Yi T;Zhao X;Wei Y
卵巢癌是全世界最致命的妇科恶性肿瘤之一，目前尚未建立令人满意的治疗方法。因此，阐明卵巢癌靶向治疗的分子机制至关重要。 PDLIM2 对于促进核 p65 泛素化至关重要，因此它在炎症中的作用最近得到了强调。我们证明，与正常卵巢组织和人卵巢表面上皮细胞（HOSE）相比，PDLIM2 在卵巢高级别浆液性癌和各种人卵巢癌细胞系中均减少。进一步的功能分析表明，PDLIM2 在卵巢癌的发展中受到表观遗传抑制，并且 PDLIM2 的抑制通过 NOS2 衍生的一氧化氮信号传导在体内和体外促进卵巢癌的生长，从而导致 M2 型巨噬细胞的募集。这些结果表明PDLIM2可能参与卵巢癌的发病机制，这可以作为卵巢癌患者有希望的治疗靶点。
Ovarian cancer constitutes one of the most lethal gynaecological malignancies worldwide and currently no satisfactory therapeutic approaches have been established. Therefore, elucidation of molecular mechanisms to develop targeted therapy of ovarian cancer is crucial. PDLIM2 is critical to promote ubiquitination of nuclear p65 and thus its role in inflammation has been highlighted recently. We demonstrate that PDLIM2 is decreased in both ovarian high-grade serous carcinoma and in various human ovarian cancer cell lines compared with normal ovary tissues and human ovarian surface epithelial cells (HOSE). Further functional analysis revealed that PDLIM2 is epigenetically repressed in ovarian cancer development and inhibition of PDLIM2 promoted ovarian cancer growth both in vivo and in vitro via NOS2-derived nitric oxide signaling, leading to recruitment of M2 type macrophages. These results suggest that PDLIM2 might be involved in ovarian cancer pathogenesis, which could serve as a promising therapeutic target for ovarian cancer patients.