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<p>Long non-coding RNAs (lncRNAs) plays critical roles in hepatocellular carcinoma (HCC), but their post-transcriptional regulation via N6-methyladenosine (m6A) remains poorly understood. Here, we identify NRAV as an m6A-modified lncRNA that promotes HCC stemness through a defined molecular axis. Integrating bioinformatics analysis of TCGA data with in vitro and in vivo validation, we demonstrated that NRAV is significantly overexpressed in HCC and associated with poor prognosis. Mechanistically, NRAV acts as a competing endogenous RNA (ceRNA), sequestering hsa-let-7c-5p and preventing it from downregulating LIN28B, a key stemness factor. This leads to increased LIN28B protein levels and enhanced expression of cancer stem cell markers. MeRIP-qPCR and site-directed mutagenesis experiments confirm that m6A modification of NRAV is crucial for its function. In animal models and clinical tissues, NRAV expression correlates with disease progression and CSC marker accumulation. Our findings uncover a novel NRAV-let-7c-5p-LIN28B axis that links m6A modification to CSC maintenance in HCC, highlighting a potential therapeutic target for disrupting stemness pathways in liver cancer.</p><p></p>

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NRAV promotes HCC stemness via the m6A-regulated let-7c-5p/LIN28B axis

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年12月12日

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  • Yuhang Chen,
  • Suoyi Dai,
  • Liping Zhuang,
  • Wenxun Cai,
  • Hao Chen,
  • Jiangang Zhao,
  • Fenglin Zhang,
  • Lianyu Chen,
  • Chien-Shan Cheng

摘要

Long non-coding RNAs (lncRNAs) plays critical roles in hepatocellular carcinoma (HCC), but their post-transcriptional regulation via N6-methyladenosine (m6A) remains poorly understood. Here, we identify NRAV as an m6A-modified lncRNA that promotes HCC stemness through a defined molecular axis. Integrating bioinformatics analysis of TCGA data with in vitro and in vivo validation, we demonstrated that NRAV is significantly overexpressed in HCC and associated with poor prognosis. Mechanistically, NRAV acts as a competing endogenous RNA (ceRNA), sequestering hsa-let-7c-5p and preventing it from downregulating LIN28B, a key stemness factor. This leads to increased LIN28B protein levels and enhanced expression of cancer stem cell markers. MeRIP-qPCR and site-directed mutagenesis experiments confirm that m6A modification of NRAV is crucial for its function. In animal models and clinical tissues, NRAV expression correlates with disease progression and CSC marker accumulation. Our findings uncover a novel NRAV-let-7c-5p-LIN28B axis that links m6A modification to CSC maintenance in HCC, highlighting a potential therapeutic target for disrupting stemness pathways in liver cancer.