胰岛素样生长因子2mrna结合蛋白2通过与M6A甲基化修饰的下游靶基因CCL20和c-MYC结合在调节三阴性乳腺癌进展中的作用

IF 2 4区 医学 Q3 PHYSIOLOGY
Journal of Physiology and Pharmacology Pub Date : 2025-02-01 Epub Date: 2025-03-18 DOI:10.26402/jpp.2025.1.10
X Xu, Y Liu, C Dong, B Ma, M Sun, H Li, X Song
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引用次数: 0

摘要

本研究的目的是探讨胰岛素样生长因子2 mrna结合蛋白2 (IGF2BP2)与下游靶基因相互作用影响三阴性乳腺癌(TNBC)进展的机制。这项研究涉及了从不同类型的乳腺癌肿瘤和良性乳腺肿瘤中收集的总共80个组织样本。采用实时定量反转录PCR (real-time quantitative reverse transcription PCR, qRT-PCR)检测IGF2BP2基因在样品中的表达水平。检测IGF2BP2转染后人乳腺癌细胞(MBA-MD-231)的细胞增殖、凋亡、迁移和侵袭能力,以及CCL20和c-MYC的表达。采用RNA免疫沉淀- qrt - pcr (RIP-qRT-PCR)检测IGF2BP2与CCL20和c-MYC mRNA的结合以及IGF2BP2过表达后CCL20和c-MYC甲基化水平。结果发现:1)与乳腺良性肿瘤组相比,IGF2BP2在乳腺癌各亚型中的表达均升高,HER-2过表达组与TNBC组差异有统计学意义;2) IGF2BP2能够促进细胞的增殖、侵袭和迁移能力。值得注意的是,IGF2BP2过表达的实验组细胞凋亡率无显著差异,而IGF2BP2沉默的实验组细胞凋亡率显著升高。IGF2BP2上调CCL20和c-MYC的表达,与两者直接结合,IGF2BP2过表达后CCL20和c-MYC的甲基化水平显著升高。我们的研究结果表明,IGF2BP2在不同的乳腺癌分子亚型中表现出差异表达,在三阴性和HER-2过表达的乳腺癌中显著上调。IGF2BP2可促进TNBC的增殖、侵袭和迁移,对细胞凋亡无明显影响。通过直接结合CCL20和c-MYC,它通过提高这两个靶基因的甲基化水平来调节TNBC的进展。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Role of insulin-like growth factor 2 mRNA binding protein 2 in regulating the progression of triple-negative breast cancer via binding with M6A methylation modified downstream target genes CCL20 and c-MYC.

The objective of this study was to investigate the mechanism by which insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) interacts with downstream target genes to influence the progression of triple-negative breast cancer (TNBC). The study involved a total of 80 tissue samples collected from various types of breast cancer tumors and benign breast tumors. The gene expression levels of IGF2BP2 in the samples were quantified using real-time quantitative reverse transcription PCR (qRT-PCR). The abilities of cell proliferation, apoptosis, migration, and invasion in human breast cancer cells (MBA-MD-231), as well as the expression of CCL20 and c-MYC following IGF2BP2 transfection, were measured. The binding of IGF2BP2 to CCL20 and c-MYC mRNA and the methylation levels of CCL20 and c-MYC after IGF2BP2 overexpression were detected using RNA immunoprecipitation-qRT-PCR (RIP-qRT-PCR). As a result, we found: 1) the expression of IGF2BP2 was elevated in all subtypes of breast cancer compared to the benign breast tumor group, with significant differences in the HER-2 overexpression and TNBC groups; 2) IGF2BP2 could promote cell proliferation, invasion, and migration capabilities. Notably, there was no significant difference in apoptosis rate in the experimental group with IGF2BP2 overexpression, while the apoptosis rate significantly increased in the experimental group where IGF2BP2 was silenced. The IGF2BP2 upregulated the expression of CCL20 and c-MYC, directly binding with both, with a significant increase in the methylation levels of CCL20 and c-MYC following IGF2BP2 overexpression. Our results indicate that IGF2BP2 exhibited differential expression across different molecular subtypes of breast cancer, with notable upregulation in triple-negative and HER-2 overexpression breast cancers. IGF2BP2 was found to promote the proliferation, invasion, and migration of TNBC, with no significant effect on apoptosis. By directly binding to CCL20 and c-MYC, it played a role in regulating the progression of TNBC by enhancing the methylation levels of both of these target genes.

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来源期刊
CiteScore
4.00
自引率
22.70%
发文量
0
审稿时长
6-12 weeks
期刊介绍: Journal of Physiology and Pharmacology publishes papers which fall within the range of basic and applied physiology, pathophysiology and pharmacology. The papers should illustrate new physiological or pharmacological mechanisms at the level of the cell membrane, single cells, tissues or organs. Clinical studies, that are of fundamental importance and have a direct bearing on the pathophysiology will also be considered. Letters related to articles published in The Journal with topics of general professional interest are welcome.
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