A growing body of evidence shows that vasculogenic mimicry (VM) is closely related to the invasion and metastasis of many tumor cells. Although the estrogen receptor (ER) can promote initiation and progression of renal cell carcinoma (RCC), how the downstream biomolecules are involved, and the detailed mechanisms of how ER expression is elevated in RCC remain to be further elucidated. Here, we discovered that long noncoding RNA (LncRNA)-SERB is highly expressed in tumor cells of RCC patients. We used multiple RCC cells and an mouse model for our study, and results indicated that LncRNA-SERB could boost RCC VM formation and cell invasion and . Although a previous report showed that ERβ can affect the VM formation in RCC, it is unclear which factor could upregulate ERβ. This is the first study to show LncRNA-SERB can be the upstream regulator of ERβ to control RCC progression. Mechanistically, LncRNA-SERB may increase ERβ binding to the promoter area, and ERβ functions through transcriptional regulation of zinc finger E-box binding homeobox 1 (ZEB1) to regulate VM formation. These results suggest that LncRNA-SERB promotes RCC cell VM formation and invasion by upregulating the ERβ/ZEB1 axis and that therapeutic targeting of this newly identified pathway may better inhibit RCC progression.

中文翻译：

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LncRNA-SERB促进肾细胞癌血管生成拟态（VM）形成和肿瘤转移


越来越多的证据表明，血管生成拟态（VM）与许多肿瘤细胞的侵袭和转移密切相关。虽然雌激素受体（ER）可以促进肾细胞癌（RCC）的发生和进展，但下游生物分子如何参与，以及RCC中ER表达升高的详细机制仍有待进一步阐明。在这里，我们发现长非编码RNA（LncRNA）-SERB在RCC患者的肿瘤细胞中高表达。我们使用多个 RCC 细胞和小鼠模型进行研究，结果表明 LncRNA-SERB 可以促进 RCC VM 形成和细胞侵袭。尽管之前的报道表明ERβ可以影响RCC中VM的形成，但尚不清楚哪些因素可以上调ERβ。这是第一个研究表明 LncRNA-SERB 可以作为 ERβ 的上游调节因子来控制 RCC 进展。从机制上讲，LncRNA-SERB可能会增加ERβ与启动子区域的结合，而ERβ通过锌指E盒结合同源框1（ZEB1）的转录调节来调节VM形成。这些结果表明，LncRNA-SERB 通过上调 ERβ/ZEB1 轴促进 RCC 细胞 VM 形成和侵袭，并且针对这一新发现的途径的治疗靶向可能更好地抑制 RCC 进展。