MiR-625-5p 通过调控 M6A 去甲基化酶 ALKBH5 调节胃癌细胞的转移和增殖

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Accounts of Chemical Research Pub Date : 2024-05-28 DOI:10.2174/0115734110290125240520062925

Wenjun Jiang, Xiaodi Guo, Shanbo Ma, Yuanhong Chang, Ya Li

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引用次数: 0

摘要

背景：胃癌是一种全球流行的恶性肿瘤，转移和复发是导致晚期胃癌患者生存率下降的主要原因。尽管对胃癌的发病机制进行了大量研究，但 m6A 去甲基化酶 ALKBH5 在胃癌发病和进展过程中的重要作用已被证实，但其确切机制仍不完全清楚。研究方法免疫组化法评估胃癌组织中 ALKBH5 的表达，RT-qPCR 和 WB 法分析细胞中 ALKBH5 的表达。此外，还使用 EpiQuikTM m6A 甲基化定量检测试剂盒评估了 RNA 中的 m6A 甲基化水平。利用 CCK-8 和 Transwell 细胞检测法分别评估了胃癌细胞的增殖潜能和转移潜能。通过 TargetScan 网站预测了 miR-625-5p 与 ALKBH5 的结合位点，并用双荧光素酶报告实验证实了这种相互作用。结果研究结果表明，胃癌细胞中 m6A 甲基化水平明显增加，同时 ALKBH5 的表达量大幅下降。ALKBH5 能抑制胃癌细胞的增殖和转移。此外，研究还验证了 miR- 625-5p 与 ALKBH5 mRNA 的 3'-UTR 相互作用，从而抑制了 ALKBH5 的表达。结论通过与 ALKBH5 的特异性相互作用，miR-625-5p 调节了胃癌细胞的增殖和转移潜能，在 miR-625-5p 和 ALKBH5 之间架起了一座以前未曾探索过的胃癌发病机制的桥梁。这一发现表明，miR- 625-5p 可以成为治疗胃癌的潜在靶点，从而提高患者的预后和生活质量。

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MiR-625-5p Modulates the Metastasis and Proliferation of Gastric Cancer Cells by Governing the M6A Demethylase ALKBH5

Background: Gastric cancer is a prevalent malignant tumor globally, with metastasis and recurrence serving as primary contributors to the diminished survival rates observed in patients with advanced stages of the disease. Despite numerous investigations into the pathogenesis of gastric cancer, the significance of m6A demethylase ALKBH5 in the initiation and progression of the disease has been established, yet its precise mechanism remains incompletely understood. Methods: Immunohistochemistry was utilized for the evaluation of ALKBH5 expression in gastric cancer tissues, while RT-qPCR and WB were employed for the analysis of ALKBH5 expression in cells. Additionally, the levels of m6A methylation in RNA were assessed using the EpiQuikTM m6A methylation quantitative assay kit. The proliferative and metastatic potentials of gastric cancer cells were assessed using the CCK-8 and Transwell cell assays, respectively. The binding site between miR-625-5p and ALKBH5 was predicted through the TargetScan website, and the interaction was confirmed using a dual luciferase reporter assay. Results: The research findings indicated a significant increase in m6A methylation levels in gastric cancer cells, concomitant with a substantial decrease in ALKBH5 expression. ALKBH5 can inhibit the proliferation and metastasis of gastric cancer cells. Additionally, the interaction between miR- 625-5p and the 3'-UTR of ALKBH5 mRNA, resulting in the suppression of ALKBH5 expression, was validated. Conclusions: Through its specific interaction with ALKBH5, miR-625-5p modulates the proliferation and metastatic potential of gastric cancer cells, bridging a previously unexplored link in the pathogenesis of gastric cancer between miR-625-5p and ALKBH5. This finding suggests that miR- 625-5p could be a potential target for treating gastric cancer, with the goal of enhancing patient outcomes and quality of life.

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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.