Recent studies indicated that the estrogen receptor beta (ERβ) could affect the progression of prostate and bladder tumors, however, its roles in the renal cell carcinoma (RCC), remain to be elucidated. Here, we provide clinical evidence that ERβ expression is correlated in a negative manner with the overall survival/disease-free survival in RCC patients. Mechanism dissection revealed that targeting ERβ with ERβ-shRNA and stimulating the transactivation of ERβ with 17β-estradiol or environmental endocrine disrupting chemicals, all resulted in altering the lncRNA HOTAIR expression. The ERβ-modulated HOTAIR is able to function via antagonizing several microRNAs, including miR-138, miR-200c, miR-204, or miR-217 to impact various oncogenes, including ADAM9, CCND2, EZH2, VEGFA, VIM, ZEB1, and ZEB2, to promote RCC proliferation and invasion. Together, the identification of the ERβ-HOTAIR axis may provide us new biomarkers and/or therapeutic targets to better suppress RCC progression in the future.

中文翻译：

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雌激素受体β通过调节LncRNA HOTAIR-miR-138 / 200c / 204/217相关的CeRNA网络来促进肾细胞癌的进展。

最近的研究表明，雌激素受体β（ERβ）可能会影响前列腺和膀胱肿瘤的进展，但是，其在肾细胞癌（RCC）中的作用尚待阐明。在这里，我们提供了临床证据，表明ERβ表达与RCC患者的总生存期/无疾病生存期呈负相关。机制剖析显示，以ERβ-shRNA靶向ERβ并以17β-雌二醇或破坏环境内分泌的化学物质刺激ERβ的反式激活，均导致了lncRNA HOTAIR表达的改变。ERβ调节的HOTAIR能够通过拮抗包括miR-138，miR-200c，miR-204或miR-217在内的几种microRNA来影响各种致癌基因，包括ADAM9，CCND2，EZH2，VEGFA，VIM，ZEB1和ZEB2，促进RCC的增殖和侵袭。一起，