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环状 RNA-ABCB10 通过海绵吸附 miR-1915-3p 来上调 Rac1 促进胃癌进展。

CircRNA-ABCB10 promotes gastric cancer progression by sponging miR-1915-3p to upregulate RaC1.

机构信息

Department of Clinical Laboratory, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an City, Shaanxi Province 710061, PR China.

Department of General Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an City, Shaanxi Province 710061, PR China.

出版信息

Dig Liver Dis. 2022 Jul;54(7):896-904. doi: 10.1016/j.dld.2021.12.001. Epub 2022 Jan 3.

Abstract

BACKGROUND

Gastric cancer (GC) is a common malignant tumor of the digestive system. Increasing reports have demonstrated the crucial roles of circRNAs in tumorigenesis and progression of GC.

METHODS

The relative expression of circ-ABCB10 in GC tissues and cell lines was detected by qRT-PCR. A series of in vitro assays and a xenograft model in vivo were applied to explore the function of circ-ABCB10 in GC cells.

RESULTS

Circ-ABCB10 expression was upregulated in GC tissues and cell lines and positively correlated with poor survival of GC patients. Circ-ABCB10 downregulation decreased cell viability, inhibited cell growth, invasion, and migration, while promoted cell apoptosis of GC cell lines SGC-7901 and MKN-48. Circ-ABCB10 could upregulate Rac1 expression by directly sponging miR-1915-3p. Rescue experiments revealed that miR-1915-3p inhibitor obviously reversed the inhibitory effect of si-circ-ABCB10, and Rac1 overexpression obviously reversed the inhibitory effect of miR-1915-3p mimics on cell growth, invasion, migration, apoptosis, and cell cycle progression. Moreover, si-circ-ABCB10 effectively inhibited tumor growth in a xenograft model.

CONCLUSIONS

Our study revealed that circ-ABCB10 promoted GC progression via targeting the miR-1915-3p/Rac1 axis, and circ-ABCB10 might be a potential target for GC diagnosis and treatment.

摘要

背景

胃癌(GC)是消化系统常见的恶性肿瘤。越来越多的报道表明 circRNAs 在 GC 的发生发展中起关键作用。

方法

采用 qRT-PCR 检测 GC 组织和细胞系中 circ-ABCB10 的相对表达。应用一系列体外实验和体内异种移植模型来探讨 circ-ABCB10 在 GC 细胞中的功能。

结果

circ-ABCB10 在 GC 组织和细胞系中表达上调,与 GC 患者的不良生存呈正相关。circ-ABCB10 的下调降低了细胞活力,抑制了 GC 细胞系 SGC-7901 和 MKN-48 的细胞生长、侵袭和迁移,同时促进了细胞凋亡。circ-ABCB10 可以通过直接海绵 miR-1915-3p 来上调 Rac1 的表达。挽救实验表明,miR-1915-3p 抑制剂明显逆转了 si-circ-ABCB10 的抑制作用,Rac1 过表达明显逆转了 miR-1915-3p 模拟物对细胞生长、侵袭、迁移、凋亡和细胞周期进程的抑制作用。此外,si-circ-ABCB10 有效地抑制了异种移植模型中的肿瘤生长。

结论

我们的研究表明,circ-ABCB10 通过靶向 miR-1915-3p/Rac1 轴促进 GC 进展,circ-ABCB10 可能是 GC 诊断和治疗的潜在靶点。

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