A large number of studies have shown that circular RNAs (circRNAs) are of great significance in the occurrence and development of colorectal cancer (CRC). The purpose of this study was to explore the mechanism of circ_0001535 in CRC. The expressions of circ_0001535, miR-433-3p and recombination signal-binding protein Jκ (RBPJ) mRNA and protein in CRC tissues and cells were detected by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot. The effect of circ_0001535 on cell proliferation was detected using the Cell Counting Kit-8 (CCK-8) assay, colony formation assay and 5-ethynyl-2′-deoxyuridine (EdU) assay. The effects of circ_0001535 on migration, invasion, angiogenesis and apoptosis were investigated by wound healing assay, transwell assay, tube formation assay and flow cytometry, respectively. The interactions between miR-433-3p and circ_0001535 or RBPJ were studied using dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Xenograft tumor assay was performed to verify the role of circ_0001535 in tumor growth in vivo. The results showed that circ_0001535 and RBPJ mRNA expression levels were up-regulated and miR-433-3p was down-regulated in CRC tissues and cells. Circ_0001535 knockdown inhibited cell proliferation, migration, invasion, angiogenesis as well as promoted apoptosis in CRC cells. After analysis, it was found that circ_0001535 acted as a competing endogenous RNA (ceRNA) to inhibit miR-433-3p and then up-regulate RBPJ in CRC cells. In addition, in vivo experiment had shown that circ_0001535 knockdown inhibited tumor growth by up-regulating miR-433-3p and inhibiting RBPJ expression. The circ_0001535/miR-433-3p/ RBPJ axis plays a catalytic role in the progression of CRC, which may provide new insights into the molecular mechanism of CRC.

大量研究表明，环状RNA（circRNA）在结直肠癌（CRC）的发生、发展中具有重要意义。本研究的目的是探讨circ_0001535在CRC中的作用机制。采用实时定量聚合酶链反应（qRT-PCR）或蛋白质印迹法检测CRC组织和细胞中circ_0001535、miR-433-3p和重组信号结合蛋白Jκ（RBPJ）mRNA和蛋白的表达。使用细胞计数试剂盒-8 (CCK-8) 测定、集落形成测定和 5-乙炔基-2'-脱氧尿苷 (EdU) 测定检测 circ_0001535 对细胞增殖的影响。分别通过伤口愈合实验、Transwell实验、成管实验和流式细胞术研究circ_0001535对迁移、侵袭、血管生成和凋亡的影响。使用双荧光素酶报告基因测定和 RNA 免疫沉淀 (RIP) 测定研究 miR-433-3p 和 circ_0001535 或 RBPJ 之间的相互作用。进行异种移植肿瘤测定以验证circ_0001535在体内肿瘤生长中的作用。结果显示，CRC组织和细胞中circ_0001535和RBPJ mRNA表达水平上调，miR-433-3p表达水平下调。Circ_0001535 敲低抑制细胞增殖、迁移、侵袭、血管生成并促进 CRC 细胞凋亡。经过分析发现，circ_0001535在CRC细胞中作为竞争性内源RNA（ceRNA）抑制miR-433-3p，进而上调RBPJ。此外，体内实验表明，circ_0001535敲低通过上调miR-433-3p并抑制RBPJ表达来抑制肿瘤生长。