Department of Urology, Jinshan Hospital, Fudan University, Shanghai 201508, China; Department of Surgery, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Department of Urology, Jinshan Hospital, Fudan University, Shanghai 201508, China.
Mol Ther. 2023 Jun 7;31(6):1705-1721. doi: 10.1016/j.ymthe.2022.08.006. Epub 2022 Aug 15.
Circular RNAs (circRNAs) are a novel class of endogenous RNAs with a covalently closed loop structure. Many circRNAs have been found to participate in cancer progression. However, the detailed generation process, functions, and related mechanisms of circRNAs in prostate cancer (PCa) remain largely unknown. In the present study, we identified circEXOC6B, a novel suppressor in the metastasis of PCa. Functionally, circEXOC6B, originating from the exocyst complex component 6B (EXOC6B) gene, inhibited migration and invasion of PCa in vitro and in vivo. Mechanistically, by acting as a protein scaffold, circEXOC6B enhanced the binding of human RNA binding motif single strand interacting protein 1 (RBMS1) and human antigen R (HuR) and further increased A-kinase anchoring protein 12 (AKAP12) expression to inhibit PCa metastasis. Unlike previous studies, we found that one pair of short inverted repeats in flanking introns at least partly promoted the circularization of circEXOC6B. Our study presents a novel mechanism for the inhibitory role of circEXOC6B in PCa metastasis and provides new insight into the molecular process of circRNA generation.
环状 RNA（circRNAs）是一类具有共价闭合环结构的新型内源性 RNA。许多 circRNAs 已被发现参与癌症的进展。然而，circRNAs 在前列腺癌（PCa）中的详细生成过程、功能和相关机制仍在很大程度上未知。在本研究中，我们鉴定了 circEXOC6B，这是一种 PCa 转移的新型抑制因子。功能上，circEXOC6B 来源于外泌体复合物成分 6B（EXOC6B）基因，抑制了 PCa 的体外和体内迁移和侵袭。从机制上讲，circEXOC6B 作为一种蛋白支架，增强了人类 RNA 结合基序单链相互作用蛋白 1（RBMS1）和人类抗原 R（HuR）的结合，并进一步增加了 A-激酶锚定蛋白 12（AKAP12）的表达，从而抑制了 PCa 的转移。与以前的研究不同，我们发现侧翼内含子中的一对短反向重复序列至少部分促进了 circEXOC6B 的环化。我们的研究提出了 circEXOC6B 抑制 PCa 转移的新机制，并为 circRNA 生成的分子过程提供了新的见解。
