BACKGROUND Clear cell renal cell carcinoma (ccRCC) is one of the most prevalent malignancies in the world, and tumor metastasis is still the main reason for disease progression. Accumulating evidence shows that SH3BGRL2 may play a key role in tumor progression and metastasis. However, the role of SH3BGRL2 in ccRCC has not been systematically investigated and remains elusive. METHODS The clinical significance of SH3BGRL2 was evaluated by bioinformatic analysis and tissue microarray (TMA) samples. SH3BGRL2 expression was determined by RT-PCR, western blot and immunohistochemistry staining. Tumor suppressive effect of SH3BGRL2 was determined by both in vitro and in vivo studies. Western blot, chromatin immunoprecipitation assay and luciferase report assay were applied for mechanism dissection. FINDINGS SH3BGRL2 was crucial for epithelial-mesenchymal transition (EMT) progression and metastasis in ccRCC. Clinically, SH3BGRL2 was identified as an independent prognostic factor for ccRCC patients. Gain- and loss-of-function results suggested that SH3BGRL2 played a critical role in cell proliferation, migration and invasion. Mechanistically, we found that SH3BGRL2 acted as a tumor suppressor through Hippo/TEAD1 signaling, then TEAD1 altered Twist1 expression at the transcriptional level via directly binding to its promoter region. INTERPRETATION Our findings established that SH3BGRL2 performed as a tumor suppressor and modulator via Hippo/TEAD1-Twist1 signaling in ccRCC, and the alteration of SH3BGRL2 could serve as a functional response biomarker of tumor progression and metastasis in ccRCC.

中文翻译：

---

SH3BGRL2通过激活河马/ TEAD1-Twist1途径抑制透明细胞肾细胞癌的生长和转移。

背景技术透明细胞肾细胞癌（ccRCC）是世界上最普遍的恶性肿瘤之一，并且肿瘤转移仍然是疾病进展的主要原因。越来越多的证据表明，SH3BGRL2可能在肿瘤的进展和转移中起关键作用。但是，SH3BGRL2在ccRCC中的作用尚未得到系统的研究，仍然难以捉摸。方法通过生物信息学分析和组织微阵列（TMA）样品评估SH3BGRL2的临床意义。通过RT-PCR，蛋白质印迹和免疫组化染色确定SH3BGRL2的表达。SH3BGRL2的肿瘤抑制作用通过体外和体内研究确定。Western blot，染色质免疫沉淀法和萤光素酶报告法用于机制解剖。结论SH3BGRL2对于ccRCC的上皮-间质转化（EMT）进展和转移至关重要。在临床上，SH3BGRL2被确定为ccRCC患者的独立预后因素。功能获得和丧失的结果表明，SH3BGRL2在细胞增殖，迁移和侵袭中发挥了关键作用。从机制上讲，我们发现SH3BGRL2通过Hippo / TEAD1信号传导起肿瘤抑制作用，然后TEAD1通过直接与其启动子区域结合，在转录水平上改变了Twist1表达。解释我们的发现建立了SH3BGRL2通过ccRCC中的Hippo / TEAD1-Twist1信号传导作为肿瘤抑制因子和调节剂，而SH3BGRL2的改变可以作为ccRCC中肿瘤进展和转移的功能性反应生物标志物。