METTL14 通过调节铁变态反应和 GPX4 的 m6A 修饰在 NSCLC 中发挥致癌作用。

IF 2.5 4区医学 Q3 ENDOCRINOLOGY & METABOLISM

Archives of Physiology and Biochemistry Pub Date : 2024-07-11 DOI:10.1080/13813455.2024.2376813

Yang Lou, Kan Huang, Bo Xu, Xianguo Chen

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引用次数: 0

摘要

背景：RNA的N6-甲基腺苷（m6A）参与了非小细胞肺癌（NSCLC）的进展：本研究探讨了METTL14在NSCLC中的作用及其机制：通过实时定量 PCR 和 ELISA 检测法评估表达水平。细胞活力通过细胞计数试剂盒-8进行评估。通过甲基化 RNA 免疫沉淀（MeRIP）、RIP、荧光素酶检测和 mRNA 稳定性检测分析 M6A 甲基化：结果表明，METTL14在NSCLC组织和细胞系中高表达。结果表明，METTL14在NSCLC组织和细胞系中高表达，敲除METTL14可抑制NSCLC细胞的活力，同时诱导NSCLC细胞的铁变态反应。从机理上讲，METTL14与GPX4相互作用，介导GPX4的m6A修饰，增强其mRNA稳定性，并上调其表达。此外，IGF2BP1 能识别经 m6A 修饰的 GPX4，并介导 mRNA 稳定性的提高。此外，GPX4还能逆转METTL14缺失的影响：METTL14/GPX4轴通过识别IGF2BP1介导的m6A修饰抑制细胞铁凋亡，从而促进NSCLC的进展。

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METTL14 plays an oncogenic role in NSCLC by modulating ferroptosis and the m6A modification of GPX4.

Context: N6-methyladenosine (m6A) of RNA is involved in the progression of non-small cell lung cancer (NSCLC).

Objective: This study investigated the role of METTL14 in NSCLC and the mechanism.

Materials and methods: Expression levels were assessed by quantitative real-time PCR and ELISA assays. Cells viability was assessed by cell counting kit-8. M6A methylation was analysed by methylated RNA immunoprecipitation (MeRIP), RIP, luciferase assay, and mRNA stability assay.

Results: The results showed that METTL14 was highly expressed in NSCLC tissues and cell lines. Knockdown of METTL14 inhibited the cell viability while induced ferroptosis of NSCLC cells. Mechanistically, METTL14 interacts with GPX4, mediates m6A modification of GPX4, enhances its mRNA stability, and upregulates its expression. In addition, IGF2BP1 recognises the m6A-methylated GPX4 and mediates the elevated mRNA stability. Moreover, GPX4 reversed the effects of METTL14 depletion.

Discussion and conclusion: The METTL14/GPX4 axis promotes NSCLC progression by inhibiting cell ferroptosis through the recognition of m6A modification mediated by IGF2BP1.

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来源期刊

Archives of Physiology and Biochemistry ENDOCRINOLOGY & METABOLISM-PHYSIOLOGY

CiteScore

6.90

自引率

3.30%

发文量

期刊介绍： Archives of Physiology and Biochemistry: The Journal of Metabolic Diseases is an international peer-reviewed journal which has been relaunched to meet the increasing demand for integrated publication on molecular, biochemical and cellular aspects of metabolic diseases, as well as clinical and therapeutic strategies for their treatment. It publishes full-length original articles, rapid papers, reviews and mini-reviews on selected topics. It is the overall goal of the journal to disseminate novel approaches to an improved understanding of major metabolic disorders. The scope encompasses all topics related to the molecular and cellular pathophysiology of metabolic diseases like obesity, type 2 diabetes and the metabolic syndrome, and their associated complications. Clinical studies are considered as an integral part of the Journal and should be related to one of the following topics: -Dysregulation of hormone receptors and signal transduction -Contribution of gene variants and gene regulatory processes -Impairment of intermediary metabolism at the cellular level -Secretion and metabolism of peptides and other factors that mediate cellular crosstalk -Therapeutic strategies for managing metabolic diseases Special issues dedicated to topics in the field will be published regularly.