Wu Shuilian, Yang Jialei, Xu Haotian, Wang Xin, Zhang Ruirui, Lu Wenmin, Yang Jie, Li Xiaofei, Chen Sixian, Zou Yunfeng, Nan Aruo
Zhejiang Provincial Key Laboratory of Medical Genetics, Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China.
Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, Guangxi Medical University, Nanning, 530021, Guangxi, China.
Cell Biol Toxicol. 2022 Feb;38(1):129-146. doi: 10.1007/s10565-021-09591-3. Epub 2021 Mar 3.
Extensive research confirmed that circRNA can play a regulatory role in various stages of tumors by interacting with various molecules. Identifying the differentially expressed circRNA in bladder cancer and exploring its regulatory mechanism on bladder cancer progression are urgent. In this study, we screened out a circRNA-circGLIS3 with a significant upregulation trend in both bladder cancer tissues and cells. Bioinformatics prediction results showed that circGLIS3 may be involved in multiple tumor-related pathways. Function gain and loss experiments verified circGLIS3 can affect the proliferation, migration, and invasion of bladder cancer cells in vitro. Moreover, silencing circGLIS3 inhibited bladder cancer cell growth in vivo. Subsequent research results indicated circGLIS3 regulated the expression of cyclin D1, a cell cycle-related protein, and cell cycle progression. Mechanically, circGLIS3 upregulates the expression of SKP1 by adsorbing miR-1273f and then promotes cyclin D1 expression, ultimately promoting the proliferation of bladder cancer cells. In summary, our study indicates that circGLIS3 plays an oncogene role in the development of bladder cancer and has potential to be a candidate for bladder cancer.
大量研究证实，环状RNA（circRNA）可通过与多种分子相互作用，在肿瘤的各个阶段发挥调控作用。鉴定膀胱癌中差异表达的circRNA并探索其对膀胱癌进展的调控机制迫在眉睫。在本研究中，我们筛选出一种在膀胱癌组织和细胞中均有显著上调趋势的circRNA——circGLIS3。生物信息学预测结果表明，circGLIS3可能参与多条肿瘤相关通路。功能获得和缺失实验证实，circGLIS3可在体外影响膀胱癌细胞的增殖、迁移和侵袭。此外，沉默circGLIS3可在体内抑制膀胱癌细胞生长。后续研究结果表明，circGLIS3调控细胞周期相关蛋白细胞周期蛋白D1的表达及细胞周期进程。机制上，circGLIS3通过吸附miR-1273f上调SKP1的表达，进而促进细胞周期蛋白D1的表达，最终促进膀胱癌细胞的增殖。总之，我们的研究表明，circGLIS3在膀胱癌发生发展中发挥癌基因作用，有潜力成为膀胱癌的候选标志物。
