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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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.

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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 Chemistry-Chemistry (all)

CiteScore

9.40

自引率

2.10%

发文量

464