BACKGROUND ERp57 dysfunction has been shown to contribute to tumorigenesis in multiple malignances. However, the role of ERp57 in clear cell renal carcinoma (ccRCC) remains unclear. METHODS Cell proliferation ability was measured by MTT and colony forming assays. Western blotting and quantitative real-time PCR (qRT-PCR) were performed to measure protein and mRNA expression. Co-immunoprecipitation (CoIP) and proximity ligation assay (PLA) were performed to detect protein-protein interaction. Chromatin immunoprecipitation (ChIP), ribonucleoprotein immunoprecipitation (RIP), and oligo pull-down were used to confirm DNA-protein and RNA-protein interactions. Promoter luciferase analysis was used to detect transcription factor activity. RESULTS Here we found ERp57 was overexpressed in ccRCC tissues, and the higher levels of ERp57 were correlated with poor survival in patients with ccRCC. In vivo and in vitro experiments showed that ccRCC cell proliferation was enhanced by ERp57 overexpression and inhibited by ERp57 deletion. Importantly, we found ERp57 positively regulated ILF3 expression in ccRCC cells. Mechanically, ERp57 was shown to bind to STAT3 protein and enhance the STAT3-mediated transcriptional activity of ILF3. Furthermore, ILF3 levels were increased in ccRCC tissues and associated with poor prognosis. Interestingly, we revealed that ILF3 could bind to ERp57 and positively regulate its expression by enhancing its mRNA stability. Furthermore, ccRCC cell proliferation was moderated via the ERp57/STAT3/ILF3 feedback loop. CONCLUSIONS In summary, our results indicate that the ERp57/STAT3/ILF3 feedback loop plays a key role in the oncogenesis of ccRCC and provides a potential therapeutic target for ccRCC treatment.

中文翻译：

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ERp57的上调通过启动STAT3 / ILF3反馈回路来促进透明细胞肾细胞癌的进展。

背景技术ERp57功能障碍已被证明可导致多种恶性肿瘤的发生。但是，ERp57在透明细胞肾癌（ccRCC）中的作用仍不清楚。方法采用MTT法和集落形成法检测细胞的增殖能力。进行了蛋白质印迹和定量实时PCR（qRT-PCR）来测量蛋白质和mRNA的表达。进行共免疫沉淀（CoIP）和邻近结扎测定（PLA）以检测蛋白质-蛋白质相互作用。染色质免疫沉淀（ChIP），核糖核蛋白免疫沉淀（RIP）和寡聚下拉被用于确认DNA-蛋白质和RNA-蛋白质的相互作用。启动子荧光素酶分析用于检测转录因子活性。结果在这里我们发现ERp57在ccRCC组织中过表达，ERp57水平较高与ccRCC患者生存率低有关。体内和体外实验表明，ERp57的过量表达可增强ccRCC细胞的增殖，而ERp57的缺失可抑制ccRCC细胞的增殖。重要的是，我们发现ERp57阳性调节ccRCC细胞中的ILF3表达。机械上，ERp57被证明与STAT3蛋白结合并增强STAT3介导的ILF3转录活性。此外，ccRCC组织中的ILF3水平升高，与预后不良有关。有趣的是，我们揭示了ILF3可以与ERp57结合并通过增强其mRNA稳定性来正向调节其表达。此外，ccRCC细胞增殖通过ERp57 / STAT3 / ILF3反馈回路得以缓解。结论总而言之，