Cao Guanghui, Zhang Chan, Tian Xiangyong, Jing Gaopeng, Zhou Xiaolin, Yan Tianzhong
Department of Urology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Zhengzhou, Henan, 450003, People's Republic of China.
Cancer Manag Res. 2021 Mar 29;13:2885-2896. doi: 10.2147/CMAR.S288229. eCollection 2021.
Dysregulation of circular RNAs (circRNAs) is associated with bladder cancer progression. Nevertheless, the mechanisms of circRNA centrosomal protein 128 (circCEP128) underlying bladder cancer progression remain poorly understood.
The levels of circCEP128, microRNA-515-5p (miR-515-5p) and syndecan-1 (SDC1) were determined via reverse transcription-quantitative polymerase chain reaction or Western blot. The effects of circCEP128, miR-515-5p and SDC1 on bladder cancer progression were investigated via MTT and colony formation assays, flow cytometry and transwell analysis and subcutaneous xenograft experiments. The interactions between miR-515-5p and circCEP128 or SDC1 were examined through bioinformatics prediction and luciferase reporter assay.
circCEP128 and SDC1 were highly expressed and miR-515-5p was low expressed in bladder cancer tissues and cells. circCEP128 knockdown hindered cell proliferation, migration and invasion and promoted cell apoptosis in bladder cancer. circCEP128 loss increased miR-515-5p expression through direct interaction in bladder cancer cells. MiR-515-5p depletion mitigated the influences of circCEP128 knockdown on bladder cancer cell phenotypes. SDC1 was a direct target of miR-515-5p. circCEP128 positively regulated SDC1 expression via miR-515-5p. MiR-515-5p restrained the malignant progression of bladder cancer cells by decreasing SDC1 expression. circCEP128 knockdown hindered the growth of bladder cancer xenograft tumors by up-regulating miR-515-5p and down-regulating SDC1.
circCEP128 knockdown hampered the tumorigenesis and progression of bladder cancer by regulating miR-515-5p/SDC1 axis in vitro and in vivo, deepening our understanding on the molecular mechanisms of circCEP128 in bladder cancer.
环状RNA（circRNAs）失调与膀胱癌进展相关。然而，circRNA中心体蛋白128（circCEP128）在膀胱癌进展中的作用机制仍知之甚少。
通过逆转录定量聚合酶链反应或蛋白质免疫印迹法检测circCEP128、微小RNA-515-5p（miR-515-5p）和多配体蛋白聚糖-1（SDC1）的水平。通过MTT法、集落形成试验、流式细胞术、Transwell分析和皮下异种移植实验研究circCEP128、miR-515-5p和SDC1对膀胱癌进展的影响。通过生物信息学预测和荧光素酶报告基因检测来研究miR-515-5p与circCEP128或SDC1之间的相互作用。
circCEP128和SDC1在膀胱癌组织和细胞中高表达，而miR-515-5p低表达。敲低circCEP128可抑制膀胱癌细胞的增殖、迁移和侵袭，并促进细胞凋亡。在膀胱癌细胞中，circCEP128缺失通过直接相互作用增加miR-515-5p的表达。miR-515-5p缺失减轻了circCEP128敲低对膀胱癌细胞表型的影响。SDC1是miR-515-5p的直接靶标。circCEP128通过miR-515-5p正向调节SDC1的表达。miR-515-5p通过降低SDC1的表达抑制膀胱癌细胞的恶性进展。敲低circCEP128通过上调miR-515-5p和下调SDC1来抑制膀胱癌异种移植瘤的生长。
在体外和体内，敲低circCEP128通过调节miR-515-5p/SDC1轴阻碍了膀胱癌的发生和进展，加深了我们对circCEP128在膀胱癌中分子机制的理解。
