METTL3-modified lncRNA DSCAM-AS1 promotes breast cancer progression through inhibiting ferroptosis.

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS
ACS Applied Bio Materials Pub Date : 2024-08-01 Epub Date: 2024-06-04 DOI:10.1007/s10863-024-10024-z
Zeming Yan, Zhongzeng Liang, Kangwei Luo, Liyan Yu, Chunyan Chen, Miao Yu, Xiaojing Guo, Mingyi Li
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引用次数: 0

Abstract

Numerous studies have indicated that N6-methyladenosine (m6A) and lncRNAs play pivotal roles in human cancer. However, the underlying functions and mechanisms of m6A-lncRNA in the physiological processes of breast cancer remain unclear. Here, we found that DSCAM-AS1 is an m6A-modified lncRNA that was overexpressed in breast cancer tissues and cells, indicating poor clinical prognosis. Gain/loss functional assays suggested that DSCAM-AS1 inhibited erastin-induced ferroptosis in breast cancer cells. Mechanistically, there were remarkable m6A modification sites on both the 3'-UTR of DSCAM-AS1 and the endogenous antioxidant factor SLC7A11. M6A methyltransferase methyltransferase-like 3 (METTL3) methylated both SLC7A11 and DSCAM-AS1. Moreover, DSCAM-AS1 recognized m6A sites on the SLC7A11 mRNA, thereby enhancing its stability. Taken together, these findings indicated a potential therapeutic strategy for breast cancer ferroptosis in an m6A-dependent manner.

Abstract Image

METTL3修饰的lncRNA DSCAM-AS1通过抑制铁突变促进乳腺癌的进展。
大量研究表明,N6-甲基腺苷(m6A)和lncRNA在人类癌症中发挥着关键作用。然而,m6A-lncRNA在乳腺癌生理过程中的潜在功能和机制仍不清楚。在这里,我们发现DSCAM-AS1是一种m6A修饰的lncRNA,它在乳腺癌组织和细胞中过表达,预示着不良的临床预后。功能测试表明,DSCAM-AS1可抑制麦拉宁诱导的乳腺癌细胞铁突变。从机理上讲,DSCAM-AS1的3'-UTR和内源性抗氧化因子SLC7A11上都有显著的m6A修饰位点。M6A甲基转移酶甲基转移酶样3(METTL3)将SLC7A11和DSCAM-AS1都甲基化了。此外,DSCAM-AS1 还能识别 SLC7A11 mRNA 上的 m6A 位点,从而增强其稳定性。综上所述,这些研究结果表明了一种以 m6A 依赖性方式治疗乳腺癌铁突变的潜在治疗策略。
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
ACS Applied Bio Materials
ACS Applied Bio Materials Chemistry-Chemistry (all)
CiteScore
9.40
自引率
2.10%
发文量
464
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