Colorectal cancer (CRC) has been listed as the fourth deadly cancer. Circular RNA hsa_circRNA_001046, also termed as hsa_circ_0000395 (circ_0000395), has been shown to be upregulated in CRC. Nevertheless, the function of circ_0000395 in CRC progression is unclear. 42 CRC patients were enrolled in the study. Detection of circ_0000395 expression in tissues and cells was executed using real-time quantitative polymerase chain reaction (RT-qPCR). Evaluation of circ_0000395 function was performed using loss-of-function experiments in vitro and in vivo. The regulatory mechanism of circ_0000395 was predicted by bioinformatics analysis and validated by dual-luciferase reporter and RIP assays. Exosomes were isolated by ultracentrifugation and validated by western blotting, TEM, and NTA. Circ_0000395 was strongly expressed in CRC samples and cell lines. Also, circ_0000395 repressed CRC growth in mouse models in vivo and induced CRC cell apoptosis, restrained CRC cell proliferation, migration, invasion, and EMT in vitro. Mechanistically, circ_0000395 sequestered miR-432-5p to regulate MYH9 expression. Furthermore, miR-432-5p knockdown reversed circ_0000395 silencing-mediated effects on CRC cell malignant phenotypes. MYH9 overexpression counteracted the inhibiting effects of miR-432-5p upregulation on CRC cell malignant phenotypes. Additionally, CRC cells derived from exosomal circ_0000395 promoted cancer cell malignant phenotypes. Our findings demonstrated that circ_0000395 sequestered miR-432-5p to elevate MYH9 expression, resulting in facilitating CRC progression, manifesting a potential therapeutic target for CRC.

结直肠癌（CRC）已被列为第四大致命癌症。环状 RNA hsa_circRNA_001046，也称为 hsa_circ_0000395 (circ_0000395)，已被证明在 CRC 中上调。然而，circ_0000395 在 CRC 进展中的功能尚不清楚。42 名 CRC 患者参加了这项研究。使用实时定量聚合酶链反应 (RT-qPCR) 检测组织和细胞中的 circ_0000395 表达。使用体外和体内功能丧失实验对 circ_0000395 功能进行评估。通过生物信息学分析预测了 circ_0000395 的调控机制，并通过双荧光素酶报告基因和 RIP 检测对其进行了验证。通过超速离心分离外泌体，并通过蛋白质印迹、TEM 和 NTA 进行验证。Circ_0000395 在 CRC 样品和细胞系中强烈表达。还，circ_0000395 在体内小鼠模型中抑制 CRC 生长并诱导 CRC 细胞凋亡，在体外抑制 CRC 细胞增殖、迁移、侵袭和 EMT。从机制上讲，circ_0000395 隔离 miR-432-5p 以调节 MYH9 表达。此外，miR-432-5p 敲低逆转了 circ_0000395 沉默介导的对 CRC 细胞恶性表型的影响。MYH9 过表达抵消了 miR-432-5p 上调对 CRC 细胞恶性表型的抑制作用。此外，来自外泌体 circ_0000395 的 CRC 细胞促进了癌细胞的恶性表型。我们的研究结果表明，circ_0000395 隔离 miR-432-5p 以提高 MYH9 表达，从而促进 CRC 进展，显示出 CRC 的潜在治疗靶点。