Department of Oncology, The First Affiliated Hospital, College of Medicine Xi'an Jiaotong University, Xi'an, 710061, PR China.
Department of Radiation Oncology, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, 450000, PR China.
Cancer Gene Ther. 2021 Dec;28(12):1312-1324. doi: 10.1038/s41417-020-00280-7. Epub 2021 Feb 2.
Gastric cancer is the third leading cause of cancer-related death worldwide, with relapse and metastasis being major contributors to the mortality. Circular RNAs (circRNAs) have been at the center of several researches and some circRNAs have been indicated to be involved in gastric cancer as sponges. Nevertheless, the mechanism underlying the function of circRNA remains largely unclear. Therefore, this study was conducted with the main objective of screening the associated circRNA in gastric cancer and exploring its mechanism. Expression of hsa_circRNA_0009172 was validated in gastric cancer tissues and cell lines after the correlation between hsa_circRNA_0009172 and prognosis was determined. Moreover, the binding site between miR-485-3p and hsa_circRNA_0009172 or NTRK3 was verified using dual luciferase assay and RNA pull down. Function-gain and -loss experiments were performed for the purpose of detecting the effect of hsa_circRNA_0009172 in vivo and in vitro as well as its mechanism with microRNA (miRNA)-485-3p and NTRK3 in gastric cancer. The hsa_circRNA_0009172 expression was downregulated in gastric cancer tissues and cell lines, indicating a positive association with patient prognosis. Functionally, hsa_circ_0009172 overexpression inhibited proliferative, invasive and migrative potential of gastric cancer cells as well as epithelial-mesenchymal transition (EMT)-related proteins by sponging miR-485-3p to inhibit NTRK3, while miR-485-3p overexpression could reverse the inhibitory effect of hsa_circ_0009172 on gastric cancer. Furthermore, either up-regulation of hsa_circ_0009172 or down-regulation of miR-485-3p led to the suppression of xenograft tumor growth in nude mice. In conclusion, hsa_circ_0009172 serves as a tumor suppressor in gastric cancer by targeting miR-485-3p/NTRK3 axis.
胃癌是全球癌症相关死亡的第三大主要原因，复发和转移是导致死亡率的主要因素。环状 RNA（circRNA）一直是多项研究的中心，一些 circRNA 已被证明作为海绵参与胃癌。然而，circRNA 功能的机制在很大程度上仍不清楚。因此，本研究旨在筛选胃癌相关的环状 RNA，并探讨其机制。在确定 hsa_circRNA_0009172 与预后的相关性后，验证了 hsa_circRNA_0009172 在胃癌组织和细胞系中的表达。此外，使用双荧光素酶报告基因检测和 RNA 下拉实验验证了 miR-485-3p 和 hsa_circRNA_0009172 或 NTRK3 之间的结合位点。进行功能增益和功能丧失实验，目的是检测 hsa_circRNA_0009172 在体内和体外的作用及其与胃癌中 microRNA（miRNA）-485-3p 和 NTRK3 的机制。hsa_circRNA_0009172 在胃癌组织和细胞系中的表达下调，提示其与患者预后呈正相关。功能上，hsa_circ_0009172 过表达通过海绵 miR-485-3p 抑制 NTRK3 抑制胃癌细胞的增殖、侵袭和迁移能力以及上皮-间质转化（EMT）相关蛋白，而过表达 miR-485-3p 可逆转 hsa_circ_0009172 对胃癌的抑制作用。此外，上调 hsa_circ_0009172 或下调 miR-485-3p 均可抑制裸鼠异种移植瘤的生长。总之，hsa_circ_0009172 通过靶向 miR-485-3p/NTRK3 轴在胃癌中起肿瘤抑制作用。
