METTL3修饰的lncRNA DSCAM-AS1通过抑制铁突变促进乳腺癌的进展。

IF 2.9 4区 生物学 Q2 BIOPHYSICS
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

摘要

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。

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

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

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.

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来源期刊
CiteScore
6.00
自引率
0.00%
发文量
22
审稿时长
6-12 weeks
期刊介绍: The Journal of Bioenergetics and Biomembranes is an international journal devoted to the publication of original research that contributes to fundamental knowledge in the areas of bioenergetics, biomembranes, and transport, including oxidative phosphorylation, photosynthesis, muscle contraction, as well as cellular and systemic metabolism. The timely research in this international journal benefits biophysicists, membrane biologists, cell biologists, biochemists, molecular biologists, physiologists, endocrinologists, and bio-organic chemists.
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