m6A依赖的RBM15和HNRNPH1调控DGUOK-AS1在肺腺癌中的作用

m6A-dependent regulation of DGUOK-AS1 by RBM15 and HNRNPH1 in lung adenocarcinoma.

期刊: iScience
PMID: 42603931
原文: PubMed ↗
发布日期: 2026-08-16

作者

Menghao Yang — Department of Biochemistry and Molecular Biology, Binzhou Medical University, Yantai, Shandong, China.
Jiaen Wu — Department of Biochemistry and Molecular Biology, Binzhou Medical University, Yantai, Shandong, China.
Youjie Li — Department of Biochemistry and Molecular Biology, Binzhou Medical University, Yantai, Shandong, China.
Hui Li — Department of Biochemistry and Molecular Biology, Binzhou Medical University, Yantai, Shandong, China.
Hongrong Zhang — Department of Biochemistry and Molecular Biology, Binzhou Medical University, Yantai, Shandong, China.
Yan Liang — Department of Biochemistry and Molecular Biology, Binzhou Medical University, Yantai, Shandong, China.
Qin Wang — Department of Biochemistry and Molecular Biology, Binzhou Medical University, Yantai, Shandong, China.
Pingyu Wang — Department of Biochemistry and Molecular Biology, Binzhou Medical University, Yantai, Shandong, China.
Yuan Yu — Department of Biochemistry and Molecular Biology, Binzhou Medical University, Yantai, Shandong, China.
Guangbin Sun — Department of Biochemistry and Molecular Biology, Binzhou Medical University, Yantai, Shandong, China.
Jiankai Feng — Department of Laboratory Medicine, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong, China.
Wenwen Liu — Department of Endocrinology and Metabolism, Cleveland Clinic, Cleveland, OH, USA.
Shuyang Xie — Department of Biochemistry and Molecular Biology, Binzhou Medical University, Yantai, Shandong, China.
Hongfang Sun — Department of Biochemistry and Molecular Biology, Binzhou Medical University, Yantai, Shandong, China.

作者单位

Department of Biochemistry and Molecular Biology, Binzhou Medical University, Yantai, Shandong, China.
Department of Laboratory Medicine, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong, China.
Department of Endocrinology and Metabolism, Cleveland Clinic, Cleveland, OH, USA.

摘要

中文

肺腺癌（LUAD）仍然是癌症相关死亡的主要原因，因此需要更深入的分子理解。本研究探讨了长链非编码RNA脱氧鸟苷激酶反义RNA 1（DGUOK-AS1）在LUAD中的调控机制。DGUOK-AS1在LUAD细胞和血清样本中显著上调，其高表达与LUAD存在初步关联。功能实验表明，DGUOK-AS1在体内外均促进LUAD增殖和迁移，部分通过作为miR-2467-5p的竞争性内源RNA来调节PRMT5表达。机制上，RNA结合基序蛋白15（RBM15）通过m6A修饰增强DGUOK-AS1的稳定性，进而使异质性核核糖核蛋白H1（HNRNPH1）通过其RNA识别基序3（RRM3）结构域以m6A依赖性方式结合，促进降解。RBM15敲低通过miR-2467-5p/PRMT5轴减弱恶性表型。这些发现揭示了控制DGUOK-AS1稳定性的m6A依赖性机制，并提供了其对LUAD进展贡献的见解。

English

Lung adenocarcinoma (LUAD) remains a leading cause of cancer-related death, underscoring the need for an improved molecular understanding. This study investigated the regulatory mechanism of the long non-coding RNA deoxyguanosine kinase antisense RNA 1 (DGUOK-AS1) in LUAD. DGUOK-AS1 was significantly upregulated in LUAD cells and serum samples, and its elevated expression showed a preliminary association with LUAD. Functional experiments demonstrated that DGUOK-AS1 promoted LUAD proliferation and migration both in vitro and in vivo, partly by acting as a competing endogenous RNA for miR-2467-5p to modulate PRMT5 expression. Mechanistically, RNA-binding motif protein 15 (RBM15) enhanced DGUOK-AS1 stability through m6A modification, which in turn enabled heterogeneous nuclear ribonucleoprotein H1 (HNRNPH1) binding in an m6A-dependent manner via its RNA recognition motif 3 (RRM3) domain, promoting degradation. RBM15 knockdown attenuated the malignant phenotype through the miR-2467-5p/PRMT5 axis. These findings reveal an m6A-dependent mechanism governing DGUOK-AS1 stability and provide insights into its contribution to LUAD progression.

分类与指标

研究类型: 基础研究
病种: 肺癌
JCR 分区: Q1
影响因子: 4.5
新锐分区: 3区