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MiR-1915的上调通过靶向晚期糖基化终末产物受体抑制幽门螺杆菌感染的胃癌细胞的增殖、侵袭和迁移。

Up-Regulation of MiR-1915 Inhibits Proliferation, Invasion, and Migration of -Infected Gastric Cancer Cells via Targeting RAGE.

作者信息

Xu Xin Cai, Zhang Wen Bin, Li Chun Xing, Gao Hua, Pei Qi, Cao Bo Wei, He Tie Han

机构信息

Department of Gastrointestinal Tumor, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China.

出版信息

Yonsei Med J. 2019 Jan;60(1):38-47. doi: 10.3349/ymj.2019.60.1.38.

Abstract

PURPOSE

-infected gastric cancer (GC) is known to be a fatal malignant tumor, but the molecular mechanisms underlying its proliferation, invasion, and migration remain far from being completely understood. Our aim in this study was to explore miR-1915 expression and its molecular mechanisms in regulating proliferation, invasion, and migration of -infected GC cells.

MATERIALS AND METHODS

Quantitative real-time PCR and western blot analysis were performed to determine miR-1915 and receptor for advanced glycation end product (RAGE) expression in -infected GC tissues and gastritis tissues, as well as human gastric mucosal cell line GES-1 and human GC cell lines SGC-7901 and MKN45. CCK8 assay and transwell assay were performed to detect the proliferation, invasion, and migration capabilities. MiR-1915 mimics and miR-1915 inhibitor were transfected into GC cells to determine the target relationship between miR-1915 and RAGE.

RESULTS

MiR-1915 was under-expressed, while RAGE was over-expressed in -infected GC tissues and GC cells. Over-expressed miR-1915 could attenuate cellular proliferation, invasion, and migration capacities. RAGE was confirmed to be the target gene of miR-1915 by bioinformatics analysis and luciferase reporter assay. Moreover, -infected GC cellular proliferation, invasion, and migration were inhibited after treatment with pcDNA-RAGE.

CONCLUSION

MiR-1915 exerted tumor-suppressive effects on cellular proliferation, invasion, and migration of -infected GC cells via targeting RAGE, which provided an innovative target candidate for treatment of -infected GC.

摘要

目的

幽门螺杆菌感染的胃癌(GC)是一种致命的恶性肿瘤,但其增殖、侵袭和迁移的分子机制仍远未完全阐明。本研究的目的是探讨miR-1915在幽门螺杆菌感染的GC细胞中调节增殖、侵袭和迁移的表达及其分子机制。

材料与方法

采用定量实时PCR和蛋白质印迹分析,检测幽门螺杆菌感染的GC组织和胃炎组织,以及人胃黏膜细胞系GES-1和人GC细胞系SGC-7901和MKN45中miR-1915和晚期糖基化终末产物受体(RAGE)的表达。进行CCK8检测和Transwell检测以检测增殖、侵袭和迁移能力。将miR-1915模拟物和miR-1915抑制剂转染到GC细胞中,以确定miR-1915与RAGE之间的靶标关系。

结果

在幽门螺杆菌感染的GC组织和GC细胞中,miR-1915表达下调,而RAGE表达上调。过表达的miR-1915可减弱细胞的增殖、侵袭和迁移能力。通过生物信息学分析和荧光素酶报告基因检测证实RAGE是miR-1915的靶基因。此外,用pcDNA-RAGE处理后,幽门螺杆菌感染的GC细胞的增殖、侵袭和迁移受到抑制。

结论

miR-1915通过靶向RAGE对幽门螺杆菌感染的GC细胞的增殖、侵袭和迁移发挥肿瘤抑制作用,这为幽门螺杆菌感染的GC治疗提供了一个新的潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46e9/6298885/bc9401ec0dd7/ymj-60-38-g001.jpg

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