Scholarlink

<p>Esophageal squamous cell carcinoma (ESCC) is a malignancy characterized by a poor prognosis, with dysregulated lipid metabolism and chromatin remodeling playing critical roles in its pathogenesis. Small nucleolar RNAs (snoRNAs) represent a conserved family of non-coding RNAs, primarily recognized for their role in directing post-transcriptional modifications of ribosomal RNAs (rRNAs), such as 2′-O-methylation and pseudouridylation. In this study, we identified a conserved H/ACA box snoRNA, SNORA11B, significantly downregulated in ESCC tissues and patient serum samples. Functionally, SNORA11B exerts tumor-suppressive effects by inhibiting proliferation and migration of ESCC cells and promoting apoptosis. Mechanistically, through RNA pulldown assays coupled with mass spectrometry, we identified SMARCA4, a core ATPase subunit of the SWI/SNF chromatin remodeling complex, as a direct interactor of SNORA11B. We further demonstrated that SNORA11B facilitates the recruitment of SMARCA4 to the GPD1 promoter region. This recruitment increases chromatin accessibility for the transcription factor C/EBPβ, thereby enabling transcriptional activation of GPD1. The subsequent upregulation of GPD1 leads to glycerol-3-phosphate (G3P) accumulation, which induces mitochondrial compromise, ultimately contributing to the suppression of tumor progression. Clinically, high expression of SNORA11B is significantly associated with favorable prognosis in ESCC patients. Moreover, its detectable stability in serum, together with a high area under the curve (AUC) value, highlights its promising utility as a novel diagnostic biomarker. Our findings reveal a non-canonical role of SNORA11B as an epigenetic regulator and underscore the SNORA11B/GPD1 axis as a promising diagnostic target for ESCC.</p><p></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

SNORA11B recruits SWI/SNF to suppress esophageal squamous cell carcinoma malignancy by promoting GPD1-mediated G3P accumulation and mitochondrial damage

  • 期刊论文

  • 发表日期：

    2026年7月7日

查看全文
  • Lan Hu,
  • Weiqing Lu,
  • Zikun Huang,
  • Dongchen Liu,
  • Xinrui Chen,
  • Xinling Ma,
  • Zhaoyong Liu,
  • Ying Zhang

摘要

Esophageal squamous cell carcinoma (ESCC) is a malignancy characterized by a poor prognosis, with dysregulated lipid metabolism and chromatin remodeling playing critical roles in its pathogenesis. Small nucleolar RNAs (snoRNAs) represent a conserved family of non-coding RNAs, primarily recognized for their role in directing post-transcriptional modifications of ribosomal RNAs (rRNAs), such as 2′-O-methylation and pseudouridylation. In this study, we identified a conserved H/ACA box snoRNA, SNORA11B, significantly downregulated in ESCC tissues and patient serum samples. Functionally, SNORA11B exerts tumor-suppressive effects by inhibiting proliferation and migration of ESCC cells and promoting apoptosis. Mechanistically, through RNA pulldown assays coupled with mass spectrometry, we identified SMARCA4, a core ATPase subunit of the SWI/SNF chromatin remodeling complex, as a direct interactor of SNORA11B. We further demonstrated that SNORA11B facilitates the recruitment of SMARCA4 to the GPD1 promoter region. This recruitment increases chromatin accessibility for the transcription factor C/EBPβ, thereby enabling transcriptional activation of GPD1. The subsequent upregulation of GPD1 leads to glycerol-3-phosphate (G3P) accumulation, which induces mitochondrial compromise, ultimately contributing to the suppression of tumor progression. Clinically, high expression of SNORA11B is significantly associated with favorable prognosis in ESCC patients. Moreover, its detectable stability in serum, together with a high area under the curve (AUC) value, highlights its promising utility as a novel diagnostic biomarker. Our findings reveal a non-canonical role of SNORA11B as an epigenetic regulator and underscore the SNORA11B/GPD1 axis as a promising diagnostic target for ESCC.