Inhibition of IGF2BP1 attenuates the progression of endometriosis through PTBP1.

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Accounts of Chemical Research Pub Date : 2024-01-01 Epub Date: 2024-04-02 DOI:10.5603/fhc.98213

Yanlin Su, Wencai Tian, Li Cheng, Ling Yin, Xiaoxia He, Xin Wei

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引用次数: 0

Abstract

Introduction: Endometriosis (EMs), manifested by pain and infertility, is a chronic inflammatory disease. The precise pathophysiology of this disease remains uncertain. Insulin-like growth factor-2 mRNA-binding protein 1 (IGF2BP1) and polypyrimidine tract-binding protein 1 (PTBP1) have both been found to regulate proliferation, apoptosis, and invasion. This study aimed to investigate the effects of IGF2BP1/PTBP1 in treating EMs.

Materials and methods: qRT-PCR and western blotting were employed to quantify IGF2BP1 and PTBP1 expression in six patients with EMs (mean age 33.83 years). The correlation analysis, STRING database prediction, and RNA immunoprecipitation were utilized to identify the relationship between IGF2BP1 and PTBP1. Ectopic endometrial volume, weight, HE staining, and IGF2BP1 silencing were utilized to estimate the effects of IGF2BP1 in EMs model rats. qRT-PCR, CCK-8, 5-ethynyl-2'-deoxyuridine (EDU) labeling, Transwell assay, and flow cytometry were utilized to assess the effects of IGF2BP1/PTBP1 on the proliferation, migration, invasion, and apoptosis of ectopic endometrial stromal cells (eESCs). Furthermore, western blotting was employed to evaluate expressions of PCNA, VEGF, and E-cadherin in EMs rats and eESCs.

Results: The mRNA and protein levels of IGF2BP1 and PTBP1 in the ectopic and eutopic endometrium of EMs patients were significantly increased. RNA immunoprecipitation revealed a close interaction of IGF2BP1 with PTBP1. Additionally, the endometrial volume, weight, and histopathologic scores in rats were significantly reduced after IGF2BP1 silencing. IGF2BP1 silencing also decreased the expression of PCNA and VEGF, and increased E-cadherin expression in endometrial tissues of EMs rats. Moreover, IGF2BP1 silencing inhibited proliferation, migration, and invasion and promoted apoptosis through PTBP1 in eESCs.

Conclusions: IGF2BP1 exhibits potential beneficial properties in the management of EMs by interacting with PTBP1, thereby highlighting IGF2BP1 as a promising therapeutic target for EMs.

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抑制 IGF2BP1 可通过 PTBP1 减缓子宫内膜异位症的进展。

简介子宫内膜异位症（EMs）是一种慢性炎症性疾病，表现为疼痛和不孕。这种疾病的确切病理生理学仍不确定。研究发现，胰岛素样生长因子-2 mRNA结合蛋白1（IGF2BP1）和多嘧啶束结合蛋白1（PTBP1）都能调节增殖、凋亡和侵袭。本研究旨在探讨IGF2BP1/PTBP1在治疗EMs中的作用。材料与方法：采用qRT-PCR和Western印迹技术对6例EMs患者（平均年龄33.83岁）的IGF2BP1和PTBP1表达进行定量分析。通过相关性分析、STRING数据库预测和RNA免疫沉淀，确定了IGF2BP1和PTBP1之间的关系。利用异位子宫内膜体积、重量、HE染色和IGF2BP1沉默来估计IGF2BP1对EMs模型大鼠的影响。利用 qRT-PCR、CCK-8、5-乙炔基-2'-脱氧尿苷（EDU）标记、Transwell 试验和流式细胞术评估 IGF2BP1/PTBP1 对异位子宫内膜基质细胞（eESCs）增殖、迁移、侵袭和凋亡的影响。此外，还采用免疫印迹法评估了EMs大鼠和eESCs中PCNA、VEGF和E-cadherin的表达：结果：EMs患者异位和异位子宫内膜中IGF2BP1和PTBP1的mRNA和蛋白水平均显著升高。RNA免疫沉淀显示，IGF2BP1与PTBP1之间存在密切的相互作用。此外，沉默 IGF2BP1 后，大鼠子宫内膜的体积、重量和组织病理学评分均明显降低。沉默 IGF2BP1 还能降低 PCNA 和 VEGF 的表达，增加 EMs 大鼠子宫内膜组织中 E-cadherin 的表达。此外，沉默 IGF2BP1 还能抑制 eESCs 的增殖、迁移和侵袭，并通过 PTBP1 促进细胞凋亡。(Folia Histochemica et Cytobiologica 2024，第 62 卷，第 1 期，xx-xx）结论：IGF2BP1通过与PTBP1相互作用，在治疗EMs方面表现出潜在的有益特性，从而突出了IGF2BP1作为EMs治疗靶点的前景。

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.