Scholarlink

<p>N6-methyladenosine (m<sup>6</sup>A) methylation modification can influence lung adenocarcinoma (LUAD) progression by regulating gene expression. Ferroptosis, a novel regulated cell death, is involved in various malignant progression. This study aimed to elucidate the role of ferroptosis-related long non-coding RNA (lncRNA) with m<sup>6</sup>A modification in LUAD. By integrating MeRIP-seq and RNA-seq data from in-house samples and public databases, we identified that lncRNA RBMS3-AS3 was abnormally downregulated in LUAD. The low expression of RBMS3-AS3 predicted poor prognosis in LUAD patients. RBMS3-AS3 was downregulated by m<sup>6</sup>A “eraser” ALKBH5 in an m<sup>6</sup>A-dependent manner. Reduced RBMS3-AS3 expression promoted LUAD progression in vitro and in vivo through inhibiting ferroptosis. Mechanistically, RBMS3-AS3 directly bound to HNRNPDL, recruiting it from the nucleus to the cytoplasm to stabilize <i>ZEB1</i> mRNA. ZEB1 interacted with the E-box motif in the GPX4 promoter, suppressing GPX4 transcription and thereby promoting ferroptosis. In conclusion, RBMS3-AS3, epigenetically downregulated by ALKBH5, facilitates LUAD progression by inhibiting ferroptosis via the HNRNPDL/ZEB1/GPX4 axis, and may serve as a novel therapeutic target for LUAD.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

M6A-ALKBH5-dependent RBMS3-AS3 down-regulation suppresses ferroptosis to promote lung adenocarcinoma progression through HNRNPDL/ZEB1/GPX4 axis

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年11月17日

查看全文
  • Wenke Ge,
  • Qi Wang,
  • Hongshun Wang,
  • Weiran Zhang,
  • Liang Chen,
  • Zhihua Li,
  • Weibing Wu

摘要

N6-methyladenosine (m6A) methylation modification can influence lung adenocarcinoma (LUAD) progression by regulating gene expression. Ferroptosis, a novel regulated cell death, is involved in various malignant progression. This study aimed to elucidate the role of ferroptosis-related long non-coding RNA (lncRNA) with m6A modification in LUAD. By integrating MeRIP-seq and RNA-seq data from in-house samples and public databases, we identified that lncRNA RBMS3-AS3 was abnormally downregulated in LUAD. The low expression of RBMS3-AS3 predicted poor prognosis in LUAD patients. RBMS3-AS3 was downregulated by m6A “eraser” ALKBH5 in an m6A-dependent manner. Reduced RBMS3-AS3 expression promoted LUAD progression in vitro and in vivo through inhibiting ferroptosis. Mechanistically, RBMS3-AS3 directly bound to HNRNPDL, recruiting it from the nucleus to the cytoplasm to stabilize ZEB1 mRNA. ZEB1 interacted with the E-box motif in the GPX4 promoter, suppressing GPX4 transcription and thereby promoting ferroptosis. In conclusion, RBMS3-AS3, epigenetically downregulated by ALKBH5, facilitates LUAD progression by inhibiting ferroptosis via the HNRNPDL/ZEB1/GPX4 axis, and may serve as a novel therapeutic target for LUAD.