Helicobacter pylori infection induces gastric cancer cell malignancy by targeting HOXA-AS2/miR-509-3p/MMD2 axis

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Accounts of Chemical Research Pub Date : 2024-04-04 DOI:10.1007/s13258-024-01500-2

Si Cheng, Yu Jia, Juan Wu, Jiguang Li, Yan Cao

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引用次数: 0

Abstract

Background

Helicobacter pylori (Hp) infection is considered to be the strongest risk factor for gastric cancer (GC). Long non-coding RNA HOXA cluster antisense RNA 2 (HOXA-AS2) has been indicated to be significantly related to Hp infection in GC patients.

Objective

To investigate the detailed role and molecular mechanism of lncRNA HOXA-AS2 in Hp-induced GC.

Methods

GC cells were treated with Hp filtrate for cell infection. Bioinformatics tools were utilized for survival analysis and prediction of HOXA-AS2 downstream molecules. Western blotting and RT-qPCR were utilized for assessing protein and RNA levels, respectively. Flow cytometry, colony formation and CCK-8 assays were implemented for testing HOXA-AS2 functions in Hp-infected GC cells. HOXA-AS2 localization in cells was determined by subcellular fractionation assay. The relationship between RNAs were measured by luciferase reporter assay.

Results

Hp infection induced HOXA-AS2 upregulation in GC cells. Knocking down HOXA-AS2 restrained cell proliferation but promoted cell apoptosis with Hp infection. HOXA-AS2 bound to miR-509-3p, and miR-509-3p targeted monocyte to macrophage differentiation associated 2 (MMD2). Overexpressing MMD2 reversed HOXA-AS2 depletion-mediated suppression on cell aggressiveness with Hp infection.

Conclusion

Hp infection induces the aggressiveness of GC cells by regulating HOXA-AS2/miR-509-3p/MMD2 axis.

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幽门螺杆菌感染通过靶向 HOXA-AS2/miR-509-3p/MMD2 轴诱导胃癌细胞恶变

背景幽门螺杆菌（Hp）感染被认为是胃癌（GC）的最强风险因素。目的研究lncRNA HOXA-AS2在Hp诱导的GC中的具体作用和分子机制。方法用Hp滤液处理GC细胞以进行细胞感染。利用生物信息学工具对HOXA-AS2下游分子进行生存分析和预测。分别利用 Western 印迹和 RT-qPCR 评估蛋白质和 RNA 水平。流式细胞术、集落形成和CCK-8检测法用于测试HOXA-AS2在Hp感染的GC细胞中的功能。亚细胞分馏法测定了HOXA-AS2在细胞中的定位。结果Hp感染诱导HOXA-AS2在GC细胞中上调。敲除HOXA-AS2可抑制细胞增殖，但在Hp感染下可促进细胞凋亡。HOXA-AS2与miR-509-3p结合，miR-509-3p靶向单核细胞到巨噬细胞分化相关2（MMD2）。结论Hp感染通过调节HOXA-AS2/miR-509-3p/MMD2轴诱导GC细胞的侵袭性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Accounts of Chemical Research 化学-化学综合

CiteScore

31.40

自引率

1.10%

发文量

312

审稿时长

2 months

期刊介绍： Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.