Li Tong, Xu Jianguo, Liu Yi
The Department of Neurosurgery of West China Hospital of Sichuan University, Chengdu, China.
Front Cell Dev Biol. 2021 Dec 7;9:757260. doi: 10.3389/fcell.2021.757260. eCollection 2021.
An increasing number of studies have indicated that circular RNAs (circRNAs) participate in the progression of numerous tumors. However, the functions of circRNAs in glioblastoma (GBM) remain largely unknown. In this study, we focused on a novel circRNA (hsa_circRFX3_003) that was spliced from RFX3, which we named circRFX3. We confirmed that the expression of circRFX3 was substantially increased in GBM cell lines and clinical GBM tissues. The results of a series of overexpression and knockdown assays indicated that circRFX3 could boost the proliferation, invasion, and migration of GBM cells. By performing dual-luciferase reporter gene and RNA pull-down assays, we verified that circRFX3 could sponge microRNA-587 (miR-587) to exercise its function as a competing endogenous RNA (ceRNA) in the development of GBM. In addition, PDIA3 was proven to be a downstream target of miR-587 and to regulate the Wnt/β-catenin pathway. In conclusion, circRFX3 could act as a cancer-promoting circRNA to boost the development of GBM and regulate the miR-587/PDIA3/β-catenin axis. This study might provide a novel target for the treatment of GBM with molecular therapy.
越来越多的研究表明，环状RNA（circRNA）参与了多种肿瘤的进展。然而，circRNA在胶质母细胞瘤（GBM）中的功能在很大程度上仍不清楚。在本研究中，我们聚焦于一种从RFX3剪接而来的新型circRNA（hsa_circRFX3_003），我们将其命名为circRFX3。我们证实，circRFX3在GBM细胞系和临床GBM组织中的表达显著增加。一系列过表达和敲低实验结果表明，circRFX3可以促进GBM细胞的增殖、侵袭和迁移。通过进行双荧光素酶报告基因和RNA下拉实验，我们验证了circRFX3可以吸附微小RNA-587（miR-587），从而在GBM发生发展过程中作为竞争性内源RNA（ceRNA）发挥作用。此外，PDIA3被证明是miR-587的下游靶点，并调控Wnt/β-连环蛋白信号通路。总之，circRFX3可作为一种促癌circRNA促进GBM的发展，并调控miR-587/PDIA3/β-连环蛋白轴。本研究可能为GBM的分子治疗提供一个新的靶点。
