Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Unit III & Ostomy Service, Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, Beijing, 100142, China.
Department of Newborn Screening, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing, 100026, China.
Cell Death Dis. 2020 Jul 22;11(7):557. doi: 10.1038/s41419-020-02757-7.
Circular RNAs (circRNAs) are an emerging class of non-coding RNAs, identified to participate in multiple malignancies. Nevertheless, the clinical significance, biological function, and regulatory mechanisms of circRNAs in colon cancer (CC) remain largely unclear. In this study, the circRNA expression profile in CC and matched normal tissues was analyzed using circRNA microarrays. A novel circRNA, circCTNNA1, was significantly upregulated in CC, and its level was associated with advanced tumor-node-metastasis stage and poor prognosis of patients with CC. Functional experiments, including Cell Counting Kit-8, colony formation, 5-ethynyl-2'-deoxyuridine, transwell, wound healing, flow cytometric analysis, and in vivo tumorigenesis assay were then performed to investigate the oncogenic role of circCTNNA1. The results revealed that circCTNNA1 promoted CC cell proliferation, migration, and invasion in vitro and in vivo. Mechanistically, RNA pull-down, RNA immunoprecipitation, dual-luciferase reporter assays, and fluorescent in situ hybridization were performed to unveil that circCTNNA1 can serve as a competing endogenous RNA of miR-149-5p to counteract the suppressive effect of miR-149-5p on downstream target Forkhead Box M1 (FOXM1). In summary, our study demonstrated that circCTNNA1 facilitated CC proliferation and invasion via the circCTNNA1/miR-149-5p/FOXM1 axis, and it might function as a novel diagnostic or therapeutic target for patients with CC.
环状 RNA（circRNAs）是一类新兴的非编码 RNA，已被鉴定参与多种恶性肿瘤的发生。然而，circRNAs 在结肠癌（CC）中的临床意义、生物学功能和调控机制在很大程度上仍不清楚。在本研究中，我们使用 circRNA 微阵列分析了 CC 及匹配的正常组织中的 circRNA 表达谱。发现一个新型 circRNA，circCTNNA1，在 CC 中显著上调，其水平与 CC 患者的晚期肿瘤-淋巴结-转移分期和预后不良相关。然后进行了包括细胞计数试剂盒-8、集落形成、5-乙炔基-2'-脱氧尿苷、Transwell、划痕愈合、流式细胞术分析和体内肿瘤生成实验在内的功能实验，以研究 circCTNNA1 的致癌作用。结果表明，circCTNNA1 在体外和体内促进 CC 细胞的增殖、迁移和侵袭。机制研究表明，通过 RNA 下拉、RNA 免疫沉淀、双荧光素酶报告基因实验和荧光原位杂交实验揭示了 circCTNNA1 可以作为 miR-149-5p 的竞争性内源 RNA，抵消 miR-149-5p 对下游靶基因叉头框 M1（FOXM1）的抑制作用。综上所述，我们的研究表明 circCTNNA1 通过 circCTNNA1/miR-149-5p/FOXM1 轴促进 CC 的增殖和侵袭，它可能作为 CC 患者的新型诊断或治疗靶点。
