Tongji University School of Medicine, Shanghai, 200065, China; Department of Gastroenterology, The Affiliated Hospital of Medical School of Ningbo University, Ningbo, 315020, Zhejiang, China.
Department of Pediatrics, Ningbo Women & Children's Hospital, Ningbo, 315012, Zhejiang, China.
Mol Cell Probes. 2020 Aug;52:101562. doi: 10.1016/j.mcp.2020.101562. Epub 2020 Mar 16.
Gastric carcinoma (GC) is one of the most common cancers with the fifth highest incidence of malignant tumors and the second highest death rate in the world. Ever-increasing investigations have shown that circular RNAs (circRNAs) are involved in the development of numerous cancers. But so far, the recognization for circMTO1 that is realized and studied as a cancer-suppressing gene is a small part and the regulatory mechanism of circMTO1 in GC has yet to be further explored. In this study, our experimental results delineated that circMTO1 exhibited much lower expression level in GC tissues and cells. CircMTO1 overexpression slowed down GC progression via inhibiting cell proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) process. Besides, circMTO1 acted as a sponge for miR-3200-5p as well as it could negatively regulate the expression of miR-3200-5p. Moreover, circMTO1 was verified to compete with PEBP1 to bind to miR-3200-5p, thus decelerating the development of GC. In a word, this study was the first to indagate the underlying mechanism of circMTO1 in GC and confirmed circMTO1 exerted its anti-cancer effects by miR-3200-5p/PEBP1 axis, implying that circMTO1 may become a new promising therapeutic target for GC patients.
胃癌（GC）是最常见的癌症之一，其发病率在恶性肿瘤中排名第五，死亡率排名第二。越来越多的研究表明，环状 RNA（circRNA）参与了许多癌症的发生发展。但到目前为止，circMTO1 作为一种抑癌基因被认识和研究的部分还很小，circMTO1 在 GC 中的调控机制仍有待进一步探索。在本研究中，我们的实验结果表明，circMTO1 在 GC 组织和细胞中的表达水平明显降低。circMTO1 的过表达通过抑制细胞增殖、迁移、侵袭和上皮-间充质转化（EMT）过程来减缓 GC 的进展。此外，circMTO1 可以作为 miR-3200-5p 的海绵，并且可以负调控 miR-3200-5p 的表达。此外，circMTO1 被证实与 PEBP1 竞争结合 miR-3200-5p，从而减缓 GC 的发展。总之，本研究首次探讨了 circMTO1 在 GC 中的作用机制，并证实 circMTO1 通过 miR-3200-5p/PEBP1 轴发挥其抗癌作用，提示 circMTO1 可能成为 GC 患者新的有前途的治疗靶点。
