Estrogen receptor-related receptor γ uppresses hypoxia-induced angiogenesis by regulating VEGFA in endometrial cancer
Estrogen receptor-related receptor γ uppresses hypoxia-induced angiogenesis by regulating VEGFA in endometrial cancer
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DOI：
10.1080/09513590.2023.2264411
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发表时间：
2023-12-14
影响因子：
2
通讯作者：
Wang，Hong-bo
中科院分区：
文献类型：
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作者：
Wang，Xiao-xiao;Hua，Teng;Wang，Hong-bo
目的雌激素受体相关受体γ(ERRγ)与癌细胞的增殖和转移密切相关。然而，ERRγ在肿瘤血管生成中的作用尚待揭示。本研究旨在阐明ERRγ对子宫内膜癌血管生成的调节作用。方法采用免疫组织化学方法检测ERRγ、VEGFA、CD31和缺氧诱导因子-1在子宫内膜癌组织中的表达。通过转染法建立稳定表达ERRγ的人脐静脉内皮细胞-1A细胞，并进行内皮细胞管形成实验。CCK-8法检测细胞存活率，创面愈合法检测细胞迁移能力。采用免疫印迹、酶联免疫吸附试验和定量逆转录聚合酶链式反应检测VEGFA的表达。低氧处理高表达ERRγ的HEC-1A细胞后，用免疫印迹法检测ERRγ和VEGFA的表达。最后，皮下注射稳定表达ERRγ的人EC-1a细胞和对照细胞，建立裸鼠EC移植瘤。结果ERRγ的表达与血管内皮生长因子呈负相关。ERRγ过表达可显著降低裸鼠肿瘤组织中HIF-1的表达水平。ERRγ过表达下调抑制了血管生成能力，抑制了细胞的增殖和迁移。缺氧条件下ERRγ的表达被抑制，而ERRγ的恢复部分抑制了缺氧诱导的内皮细胞VEGFA的表达。结论ERRγ是一种血管生成抑制因子，参与了缺氧诱导的内皮细胞VEGFA的表达。因此，ERRγ可能是一种很有前途的抗血管生成靶点。
ObjectiveEstrogen receptor-related receptor γ (ERRγ), is implicated in cancer cell proliferation and metastasis. The function of ERRγ in tumor angiogenesis, however, is to be revealed. This study was designed to elaborate the regulatory effect of ERRγ on angiogenesis in endometrial cancer (EC).MethodsImmunohistochemistry (IHC) was adopted to determine the protein expression of ERRγ, VEGFA, CD31 and hypoxia-inducible factor-1 (HIF-1) in tumor tissues. HEC-1A cells stably expressing ERRγ were established bytransfection, and then an endothelial cell tube formation assay was performed. CCK-8 assay was employed for cell viability, and wound healing assay for cell migration ability. Besides, western blot, ELISA and qRT-PCR were used to examine the VEGFA expression. After hypoxia treatment of ERRγ overexpressing HEC-1A cells, the ERRγ expression and VEGFA expression were determined by western blot. Finally, EC xenografts in nude mice were constructed by subcutaneous injection of ERRγ stably expressing HEC-1A cells and control HEC-1A cells.ResultsIHC results revealed a negative correlation between the expression of ERRγ and VEGFA in EC tissues. ERRγ overexpression significantly decreased the level of HIF-1 in tumor tissue of nude mice. ERRγ overexpression down-regulated inhibited angiogenesis capability and inhibited the proliferation and migration of HEC-1A cells. Furthermore, ERRγ expression was suppressed under the condition of hypoxia while restoration of ERRγ partially inhibited hypoxia-induced VEGFA expression in HEC-1A cells.ConclusionsERRγ is an angiogenesis suppressor and involved in hypoxia-induced VEGFA expression in EC. Hence, ERRγ might be a promising antiangiogenic target for human EC.