IGF2BP2-mediated m6A modifies SLC7A11 to regulate proliferation and ferroptosis in non-small cell lung cancer cells.

IF 2.1 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Advances in Clinical and Experimental Medicine Pub Date : 2025-04-24 DOI:10.17219/acem/200588

Bo Li, Si-Ying Li, Yi-Chao Yan

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引用次数: 0

Abstract

Background: Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) is implicated in various cancers, but its role in modulating ferroptosis and tumor cell behavior in non-small cell lung cancer (NSCLC) remains unclear.

Objectives: This study aimed to investigate how IGF2BP2-mediated N6-methyladenosine (m6A) modification of solute carrier family 7 member 11 (SLC7A11) affects ferroptosis and NSCLC cell viability.

Material and methods: NSCLC H1299 cells were transfected with either IGF2BP2 or SLC7A11 plasmids and corresponding siRNAs. Expression levels of IGF2BP2, SLC7A11 and ferroptosis markers were analyzed using reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR) and western blot. Cell viability was assessed using the Cell Counting Kit-8 (CCK-8) assay. Reactive oxygen species (ROS) and lipid peroxidation levels were measured with flow cytometry and biochemical kits. The RNA immunoprecipitation (RIP) and mRNA stability assays were utilized to explore the interaction between IGF2BP2 and SLC7A11.

Results: IGF2BP2 expression was significantly upregulated in H1299 cells. Overexpression of IGF2BP2 enhanced cell viability and decreased ferroptosis, whereas its knockdown resulted in reduced cell viability and increased ferroptotic activity. IGF2BP2 enhanced SLC7A11 mRNA stability through m6A modification, and SLC7A11 overexpression reversed the effects of IGF2BP2 knockdown. This interaction increased cell viability and reduced ROS and lipid peroxidation.

Conclusions: IGF2BP2 plays a critical role in NSCLC by stabilizing SLC7A11 mRNA via m6A modification, promoting cell proliferation and suppressing ferroptosis. Targeting the IGF2BP2-SLC7A11 axis may offer a promising therapeutic strategy for NSCLC.

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igf2bp2介导的m6A修饰SLC7A11调节非小细胞肺癌细胞的增殖和铁凋亡。

背景：胰岛素样生长因子2 mrna结合蛋白2 （IGF2BP2）与多种癌症有关，但其在非小细胞肺癌（NSCLC）中调节铁凋亡和肿瘤细胞行为的作用尚不清楚。目的：本研究旨在探讨igf2bp2介导的溶质载体家族7成员11 (SLC7A11) n6 -甲基腺苷（m6A）修饰对铁凋亡和NSCLC细胞活力的影响。材料和方法：用IGF2BP2或SLC7A11质粒及相应的sirna转染NSCLC H1299细胞。采用逆转录实时定量聚合酶链反应（RT-qPCR）和western blot分析IGF2BP2、SLC7A11和铁下垂标志物的表达水平。采用细胞计数试剂盒-8 （CCK-8）法评估细胞活力。用流式细胞术和生化试剂盒检测活性氧（ROS）和脂质过氧化水平。利用RNA免疫沉淀（RIP）和mRNA稳定性分析来探索IGF2BP2和SLC7A11之间的相互作用。结果：IGF2BP2在H1299细胞中表达显著上调。IGF2BP2过表达可增强细胞活力，降低铁下垂，而其敲低可降低细胞活力，增加铁下垂活性。IGF2BP2通过m6A修饰增强了SLC7A11 mRNA的稳定性，SLC7A11过表达逆转了IGF2BP2敲低的作用。这种相互作用增加了细胞活力，减少了活性氧和脂质过氧化。结论：IGF2BP2通过m6A修饰稳定SLC7A11 mRNA，促进细胞增殖，抑制铁凋亡，在NSCLC中发挥关键作用。靶向IGF2BP2-SLC7A11轴可能为非小细胞肺癌的治疗提供了一种有希望的治疗策略。

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

Advances in Clinical and Experimental Medicine MEDICINE, RESEARCH & EXPERIMENTAL-

CiteScore

3.70

自引率

4.80%

发文量

153

审稿时长

6-12 weeks

期刊介绍： Advances in Clinical and Experimental Medicine has been published by the Wroclaw Medical University since 1992. Establishing the medical journal was the idea of Prof. Bogumił Halawa, Chair of the Department of Cardiology, and was fully supported by the Rector of Wroclaw Medical University, Prof. Zbigniew Knapik. Prof. Halawa was also the first editor-in-chief, between 1992-1997. The journal, then entitled "Postępy Medycyny Klinicznej i Doświadczalnej", appeared quarterly. Prof. Leszek Paradowski was editor-in-chief from 1997-1999. In 1998 he initiated alterations in the profile and cover design of the journal which were accepted by the Editorial Board. The title was changed to Advances in Clinical and Experimental Medicine. Articles in English were welcomed. A number of outstanding representatives of medical science from Poland and abroad were invited to participate in the newly established International Editorial Staff. Prof. Antonina Harłozińska-Szmyrka was editor-in-chief in years 2000-2005, in years 2006-2007 once again prof. Leszek Paradowski and prof. Maria Podolak-Dawidziak was editor-in-chief in years 2008-2016. Since 2017 the editor-in chief is prof. Maciej Bagłaj. Since July 2005, original papers have been published only in English. Case reports are no longer accepted. The manuscripts are reviewed by two independent reviewers and a statistical reviewer, and English texts are proofread by a native speaker. The journal has been indexed in several databases: Scopus, Ulrich’sTM International Periodicals Directory, Index Copernicus and since 2007 in Thomson Reuters databases: Science Citation Index Expanded i Journal Citation Reports/Science Edition. In 2010 the journal obtained Impact Factor which is now 1.179 pts. Articles published in the journal are worth 15 points among Polish journals according to the Polish Committee for Scientific Research and 169.43 points according to the Index Copernicus. Since November 7, 2012, Advances in Clinical and Experimental Medicine has been indexed and included in National Library of Medicine’s MEDLINE database. English abstracts printed in the journal are included and searchable using PubMed http://www.ncbi.nlm.nih.gov/pubmed.