生物
长非编码RNA
核糖核酸
下调和上调
癌症研究
免疫沉淀
体外
反义RNA
细胞生物学
分子生物学
细胞培养
基因
生物化学
遗传学
作者
Ying Liu,Yiwen Xia,Tianlu Jiang,Zetian Chen,Yikai Shen,Jie Lin,Li Xie,Chao Gu,Jialun Lv,Lu Chen,Diancai Zhang,Hao Xu,Li Yang,Zekuan Xu,Linjun Wang
标识
DOI:10.1038/s41419-023-05781-5
摘要
Abstract Neural invasion (NI) is a vital pathological characteristic of gastric cancer (GC), which correlates with tumor recurrence and a worse prognosis. Long noncoding RNAs (lncRNAs) play critical roles in various biological processes. However, the involvement of lncRNAs in NI of GC (GC-NI) remains unclear. DIAPH2-AS1 was upregulated in NI-positive GC tissues, which was confirmed by qRT-PCR. The higher expression of DIAPH2-AS1 predicted NI and worse survival for GC patients. Both in vitro and in vivo experiments, including wound-healing assay, Transwell assay, DRG-GC cells co-culture model, the mouse sciatic nerve model, and the lung metastasis model, indicated that DIAPH2-AS1 promoted the migration, invasion, and NI potential of GC cells. Mechanistically, pulldown assay and RNA immunoprecipitation assay revealed that DIAPH2-AS1 interacted with NSUN2. Subsequent experiments indicated that DIAPH2-AS1 stabilized NSUN2 from ubiquitin-proteasomal degradation via masking the K577 and K579 of NSUN2. The protection of DIAPH2-AS1 on NSUN2 improved the stability of NTN1 mRNA via m5C modification, which finally induced GC-NI. Our work uncovered DIAPH2-AS1 as a novel oncogenic lncRNA in GC-NI and validated the DIAPH2-AS1-NSUN2-NTN1 axis as a potential therapeutic target for NI-positive GC.
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