Department of Gastroenterology, The People's Hospital of Liaoning Province, Shenyang 110016, People's Republic of China.
Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China.
J Biochem. 2020 Aug 1;168(2):159-170. doi: 10.1093/jb/mvaa031.
Gastric cancer is one of the most common types of carcinoma with a threat to global health. MicroRNA-760 (miR-760) was significantly down-regulated in the primary tumour of patients with advanced gastric cancer. However, the role of miR-760 in gastric cancer is still unclear. Herein, miR-760 was down-regulated in gastric cancer tissues. Moreover, miR-760 overexpression and knockdown were conducted in gastric cancer cells (MGC-803 and SGC-7901) in vitro. The in vitro functional assays proved that miR-760 overexpression reduced cell viability, cell cycle, migration and invasion, promoted apoptosis and suppressed MMP activity in MGC-803 cells. Conversely, miR-760 knockdown led to the opposite in SGC-7901 cells. Notably, bone marrow stromal antigen 2 (BST2) was verified as a target gene of miR-760. MiR-760 mimics down-regulated BST2 level in gastric cancer tissues and in MGC-803 cells, whereas miR-760 inhibitor up-regulated its level in SGC-7901 cells. MiR-760-regulated cell properties through reduction of BST2. In addition, miR-760 inhibited tumourigenesis in a nude mouse xenograft model in vivo. In conclusion, our results demonstrated that miR-760 exhibited a suppressive role in gastric cancer via inhibiting BST2, indicating that miR-760/BST2 axis may provide promising therapeutic target for gastric cancer.
胃癌是最常见的癌种之一，对全球健康构成威胁。在晚期胃癌患者的原发肿瘤中，微小 RNA-760（miR-760）明显下调。然而，miR-760 在胃癌中的作用尚不清楚。本研究下调了胃癌组织中的 miR-760。此外，在体外进行了胃癌细胞（MGC-803 和 SGC-7901）中 miR-760 的过表达和敲低实验。体外功能实验证明，miR-760 过表达降低了 MGC-803 细胞的活力、细胞周期、迁移和侵袭能力，促进了细胞凋亡并抑制了 MMP 活性。相反，miR-760 敲低导致 SGC-7901 细胞出现相反的结果。值得注意的是，骨髓基质抗原 2（BST2）被证实是 miR-760 的靶基因。miR-760 模拟物下调了胃癌组织和 MGC-803 细胞中的 BST2 水平，而 miR-760 抑制剂则上调了 SGC-7901 细胞中的 BST2 水平。miR-760 通过降低 BST2 水平来调节细胞特性。此外，miR-760 在体内裸鼠异种移植模型中抑制了肿瘤发生。总之，我们的研究结果表明，miR-760 通过抑制 BST2 在胃癌中发挥抑制作用，表明 miR-760/BST2 轴可能为胃癌提供有前景的治疗靶点。
