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微小 RNA-760 在胃癌发展中作为一种肿瘤抑制因子起作用,抑制 G 蛋白偶联受体激酶相互作用蛋白-1 的转录。

MicroRNA-760 acts as a tumor suppressor in gastric cancer development inhibiting G-protein-coupled receptor kinase interacting protein-1 transcription.

机构信息

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.

出版信息

World J Gastroenterol. 2019 Dec 7;25(45):6619-6633. doi: 10.3748/wjg.v25.i45.6619.

Abstract

BACKGROUND

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.

AIM

To measure the expression level of miR-760 in GC and investigate its role in gastric tumorigenesis.

METHODS

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.

RESULTS

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.

CONCLUSION

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.

摘要

背景

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。

目的

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。

方法

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

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。

结论

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e76b/6906209/9c5df563964e/WJG-25-6619-g001.jpg

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