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MiR-485-3p/MiR-543/MiR-337-3p是结直肠癌中Hsa_circ_0007385-MEMO1轴致癌潜能所必需的。

MiR-485-3p/MiR-543/MiR-337-3p is Required for the Oncogenic Potential of the Hsa_circ_0007385-MEMO1 Axis in Colorectal Cancer.

作者信息

Yin Junfeng, Liu Guanglan, Zhu Xinguo

机构信息

Department of General Surgery, The First Affiliated Hospital of Soochow University, No. 188 Shizi Street, Gusu District, Suzhou, 215006, Jiangsu, China.

Department of General Surgery, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, 225000, Jiangsu, China.

出版信息

Biochem Genet. 2024 Apr;62(2):1182-1199. doi: 10.1007/s10528-023-10472-z. Epub 2023 Aug 10.

Abstract

Circular RNAs (circRNAs) play regulatory roles in the biological processes of multiple tumors, colorectal cancer (CRC) included. Our previous study probed the impact of circ_0007385 on CRC cell malignant behaviors, while the underlying mechanism remains obscure. In this work, the potential mechanism of hsa_circ_0007385 in CRC was probed. Functional experiments were implemented for probing the function of hsa_circ_0007385 in CRC. Further analysis revealed the relation between hsa_circ_0007385 and miRNAs. A xenograft mouse model was implemented for probing the influence of hsa_circ_0007385 on CRC growth and metastasis in vivo. Hsa_circ_0007385 was up-regulated in CRC. Hsa_circ_0007385 positively regulated its host gene mediator of cell motility 1 (MEMO1). Hsa_circ_0007385 silencing inhibited CRC progression. Hsa_circ_0007385 and MEMO1 bond to miR-485-3p/miR-543/miR-337-3p, and these three miRNAs were lowly expressed in CRC, and negatively modulated by hsa_circ_0007385. Hsa_circ_0007385 functioned as an oncogene in CRC in a miR-485-3p/miR-543/miR-337-3p- or MEMO1-dependent manner. Hsa_circ_0007385 promoted CRC progression via modulating miR-485-3p/miR-543/miR-337-3p/MEMO1 axis. Thus, circ-MEMO1 might be a promising therapeutic target for CRC.

摘要

环状RNA(circRNAs)在包括结直肠癌(CRC)在内的多种肿瘤的生物学过程中发挥调节作用。我们之前的研究探讨了circ_0007385对CRC细胞恶性行为的影响,但其潜在机制仍不清楚。在这项工作中,我们探究了hsa_circ_0007385在CRC中的潜在机制。进行了功能实验以探究hsa_circ_0007385在CRC中的功能。进一步分析揭示了hsa_circ_0007385与微小RNA(miRNAs)之间的关系。建立了异种移植小鼠模型以探究hsa_circ_0007385在体内对CRC生长和转移的影响。hsa_circ_0007385在CRC中上调。hsa_circ_0007385正向调节其宿主基因细胞运动介质1(MEMO1)。沉默hsa_circ_0007385可抑制CRC进展。hsa_circ_0007385和MEMO1与miR-485-3p/miR-543/miR-337-3p结合,这三种miRNA在CRC中低表达,并受到hsa_circ_0007385的负调控。hsa_circ_0007385在CRC中以miR-485-3p/miR-543/miR-337-3p或MEMO1依赖的方式作为癌基因发挥作用。hsa_circ_00!7385通过调节miR-485-3p/miR-543/miR-337-3p/MEMO1轴促进CRC进展。因此,circ-MEMO1可能是CRC一个有前景的治疗靶点。

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