Department of Urology, Peking University Cancer Hospital Yunnan, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.
Mol Carcinog. 2024 Apr;63(4):629-646. doi: 10.1002/mc.23677. Epub 2024 Jan 16.
Circular RNAs (circRNAs) are key in regulating bladder cancer progression. This study explored the effects of circRNA TATA-box binding protein associated factor 15 (circTAF15) on bladder cancer progression. We enrolled 80 bladder cancer patients to examine the relationship between circTAF15 expression and clinical features. The function of circTAF15 on bladder cancer cell viability, proliferation, migration, invasion, and glycolysis was monitored by cell counting kit-8 assay, 5-Ethynyl-2'-deoxyuridine experiment, Transwell experiment, and glycolysis analysis. Dual luciferase reporter gene assay, RNA pull-down assay, and RNA immunoprecipitation assay were used to verify the binding between circTAF15 and miR-502-5p or between miR-502-5p and high mobility group box 3 (HMGB3). circTAF15 effect on in vivo growth of bladder cancer was investigated by xenograft tumor experiment. Quantitative real-time polymerase chain reaction, Western blot, and immunohistochemistry were implemented to investigate the expression levels of genes. circTAF15 was upregulated in bladder cancer patients, associated with unfavorable outcomes. circTAF15 knockdown attenuated bladder cancer cell viability, proliferation, migration, invasion, epithelial-mesenchymal transition, and glycolysis. circTAF15 suppressed miR-502-5p expression, and miR-502-5p inhibited HMGB3 expression. Low miR-502-5p expression was associated with unfavorable outcomes in bladder cancer patients. miR-502-5p silencing and HMGB3 overexpression counteracted the inhibition of circTAF15 knockdown on the malignant phenotype of bladder cancer cells. circTAF15 knockdown attenuated the in vivo growth of bladder cancer cells. circTAF15 enhanced the progression of bladder cancer through upregulating HMGB3 via suppressing miR-502-5p. circTAF15 may be a novel target to treat bladder cancer in the future.
环状 RNA（circRNAs）在调控膀胱癌进展中起着关键作用。本研究探讨了环状 RNA TATA 框结合蛋白相关因子 15（circTAF15）对膀胱癌进展的影响。我们招募了 80 名膀胱癌患者，以研究 circTAF15 表达与临床特征之间的关系。通过细胞计数试剂盒-8 检测、5-乙炔基-2'-脱氧尿苷实验、Transwell 实验和糖酵解分析，监测 circTAF15 对膀胱癌细胞活力、增殖、迁移、侵袭和糖酵解的影响。双荧光素酶报告基因检测、RNA 下拉实验和 RNA 免疫沉淀实验用于验证 circTAF15 与 miR-502-5p 或 miR-502-5p 与高迁移率族蛋白 3（HMGB3）之间的结合。通过异种移植肿瘤实验研究 circTAF15 对膀胱癌体内生长的影响。实时定量聚合酶链反应、Western blot 和免疫组织化学用于检测基因的表达水平。circTAF15 在膀胱癌患者中上调，与不良结局相关。circTAF15 敲低可减弱膀胱癌细胞活力、增殖、迁移、侵袭、上皮间质转化和糖酵解。circTAF15 抑制 miR-502-5p 的表达，而 miR-502-5p 抑制 HMGB3 的表达。低 miR-502-5p 表达与膀胱癌患者的不良结局相关。miR-502-5p 沉默和 HMGB3 过表达可逆转 circTAF15 敲低对膀胱癌细胞恶性表型的抑制作用。circTAF15 敲低可减弱膀胱癌细胞在体内的生长。circTAF15 通过抑制 miR-502-5p 增强 HMGB3 的表达来促进膀胱癌的进展。circTAF15 可能成为未来治疗膀胱癌的新靶点。
