Department of Anal and Intestinal Surgery, Affiliated Hospital of Weifang Medical University, Weifang 261031, Shandong Province, China.
Department of Surgery, Weifang Medical College, Weifang 261031, Shandong Province, China.
World J Gastroenterol. 2019 Dec 7;25(45):6619-6633. doi: 10.3748/wjg.v25.i45.6619.
Gastric cancer (GC) has become a serious threat to people's health. Accumulative evidence reveals that dysregulation of numerous microRNAs (miRNAs) has been found during malignant formation. So far, the role of microRNA-760 (miR-760) in the development of GC is largely unknown.
To measure the expression level of miR-760 in GC and investigate its role in gastric tumorigenesis.
Real-time quantitative polymerase chain reaction and Western blot analysis were used to measure the expression of miR-760 and G-protein-coupled receptor kinase interacting protein-1 (GIT1). Cell growth was detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and cell colony formation assays. Apoptosis was assessed by flow cytometric analysis. The relationship between miR-760 and GIT1 was verified by luciferase reporter assay.
The results showed that the expression of miR-760 was decreased in GC and associated with poor clinical outcomes in GC patients. Furthermore, miR-760 restrained cell proliferation and cell colony formation and induced apoptosis in GC cells. In addition, miR-760 directly targeted GIT1 and negatively regulated its expression in GC. GIT1 was upregulated in GC and predicted a worse prognosis in GC patients. We also found that upregulation of GIT1 weakened the inhibitory effect of miR-760 in GC.
In conclusion, miR-760 targets GIT1 to inhibit cell growth and promote apoptosis in GC cells. Our data demonstrate that miR-760 may be a potential target for the treatment of GC.
胃癌(GC)已成为严重威胁人类健康的疾病。大量证据表明,在恶性形成过程中发现许多 microRNAs(miRNAs)失调。迄今为止,microRNA-760(miR-760)在 GC 发展中的作用在很大程度上尚不清楚。
测量 GC 中 miR-760 的表达水平并研究其在胃肿瘤发生中的作用。
实时定量聚合酶链反应和 Western blot 分析用于测量 miR-760 和 G 蛋白偶联受体激酶相互作用蛋白-1(GIT1)的表达。通过 3-(4,5-二甲基-2-噻唑基)-2,5-二苯基-2-H-四唑溴盐(MTT)和细胞集落形成测定检测细胞生长。通过流式细胞术分析评估细胞凋亡。通过荧光素酶报告测定验证 miR-760 与 GIT1 之间的关系。
结果表明,GC 中 miR-760 的表达降低,与 GC 患者的不良临床结局相关。此外,miR-760 抑制 GC 细胞的增殖和细胞集落形成并诱导细胞凋亡。此外,miR-760 直接靶向 GIT1 并负调控其在 GC 中的表达。GC 中 GIT1 上调并预测 GC 患者预后不良。我们还发现 GIT1 的上调削弱了 miR-760 在 GC 中的抑制作用。
总之,miR-760 通过靶向 GIT1 抑制 GC 细胞的生长并促进细胞凋亡。我们的数据表明,miR-760 可能是 GC 治疗的潜在靶点。