CircRNA cRAPGEF5 inhibits the growth and metastasis of renal cell carcinoma via the miR-27a-3p/TXNIP pathway
CircRNA cRAPGEF5 inhibits the growth and metastasis of renal cell carcinoma via the miR-27a-3p/TXNIP pathway
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CircRNA cRAPGEF5 通过 miR-27a-3p/TXNIP 通路抑制肾细胞癌的生长和转移。
DOI：
10.1016/j.canlet.2019.10.017
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发表时间：
2020-01-01
期刊：
影响因子：
9.7
通讯作者：
Wang, Linhui
中科院分区：
文献类型：
--
作者：
Chen, Qiong;Liu, Tao;Wang, Linhui
据报道，环状RNA（circRNA）在癌症中起重要调节剂的作用。CircRNA RAPGEF 5（cRAPGEF 5）来源于RAPGEF 5基因的外显子2-6，可促进乳头状甲状腺癌进展。然而，cRAPGEF 5在肾细胞癌（RCC）中的作用仍不清楚。在这项研究中，我们发现cRAPGEF 5在RCC组织中显著下调。在245例RCC病例中，cRAPGEF 5下调与侵袭性临床特征呈正相关，并独立预测总生存率和无复发生存率。功能测定表明，cRAPGEF 5在体外和体内抑制RCC增殖和迁移。从机制上讲，RNA免疫沉淀和circRNA体内沉淀试验表明，cRAPGEF 5作为致癌miR-27 a-3 p的海绵发挥作用，其靶向抑制基因TXNIP。通过双荧光素酶报告基因测定证实了miR-27 a-3 p与cRAPGEF 5或TXNIP之间的相互作用。总之，cRAPGEF 5通过miR-27 a-3 p/TXNIP通路在抑制RCC中发挥作用，并且可能作为RCC患者的有希望的预后生物标志物和新的治疗靶点。
Circular RNAs (circRNAs) are reported to act as important regulators in cancers. CircRNA RAPGEF5 (cRAPGEF5) is derived from exons 2-6 of the RAPGEF5 gene and may promote papillary thyroid cancer progression. However, the role of cRAPGEF5 in renal cell carcinoma (RCC) remains unclear. In this study, we found cRAPGEF5 to be significantly downregulated in RCC tissues. Among 245 RCC cases, cRAPGEF5 downregulation correlated positively with aggressive clinical characteristics and independently predicted poor overall survival and recurrence-free survival. Functional assays demonstrated that cRAPGEF5 suppresses RCC proliferation and migration in vitro and in vivo. Mechanistically, RNA Immunoprecipitation and circRNA in vivo precipitation assays showed that cRAPGEF5 functions as a sponge of oncogenic miR-27a-3p, which targets the suppressor gene TXNIP. Interactions between miR-27a-3p and cRAPGEF5 or TXNIP were confirmed by dual-luciferase reporter assays. In conclusion, cRAPGEF5 plays a role in suppressing RCC via the miR-27a-3p/TXNIP pathway and may serve as a promising prognostic biomarker and novel therapeutic target for RCC patients.