Scholarlink

<p>Small nucleolar RNA SNORD50A and SNORD50B (SNORD50A/B) have increasingly been linked to tumorigenesis due to their high frequency of deletion across multiple cancer types. However, their biological roles in non-small-cell lung cancer (NSCLC) remain to be systematically investigated. In this study, we observed that SNORD50A/B were frequently deleted in lung adenocarcinomas, and this molecular event was strongly linked to poor patient survival. Subsequent in vitro and in vivo studies demonstrated the tumor-suppressive role of SNORD50A/B in NSCLC. Mechanistically, SNORD50A/B directly bound to activating signal cointegrator 1 complex subunit 1 (ASCC1), preventing its interaction with activating signal cointegrator 1 (ASC-1) and disrupting the integrity of ASC-1 complex, which attenuates NF-κB transcriptional activity and down-regulates PD-L1 expression. Synthetic Snord50a/b-loaded cationic liposomes showed potent anti-tumor effects and sensitized NSCLC cells to anti-PD-1 immunotherapy. Taken together, SNORD50A/B exert tumor-suppressive effects by disrupting the ASC-1 complex to silence NF-κB, highlighting its therapeutic potential via cationic liposomes for treating SNORD50A/B-deficient tumors.</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

SNORD50A/B disassemble ASC-1 complex to silence NF-κB and boost PD-1 blockade in non-small-cell lung cancer

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年5月25日

查看全文
  • Jingjing Ma,
  • Qingyuan He,
  • Jun Pu,
  • Yan Liu,
  • Xiao Cui,
  • Guobin Wang,
  • Quan Chen,
  • Le Ren,
  • Mengdan Li,
  • Peng Hou

摘要

Small nucleolar RNA SNORD50A and SNORD50B (SNORD50A/B) have increasingly been linked to tumorigenesis due to their high frequency of deletion across multiple cancer types. However, their biological roles in non-small-cell lung cancer (NSCLC) remain to be systematically investigated. In this study, we observed that SNORD50A/B were frequently deleted in lung adenocarcinomas, and this molecular event was strongly linked to poor patient survival. Subsequent in vitro and in vivo studies demonstrated the tumor-suppressive role of SNORD50A/B in NSCLC. Mechanistically, SNORD50A/B directly bound to activating signal cointegrator 1 complex subunit 1 (ASCC1), preventing its interaction with activating signal cointegrator 1 (ASC-1) and disrupting the integrity of ASC-1 complex, which attenuates NF-κB transcriptional activity and down-regulates PD-L1 expression. Synthetic Snord50a/b-loaded cationic liposomes showed potent anti-tumor effects and sensitized NSCLC cells to anti-PD-1 immunotherapy. Taken together, SNORD50A/B exert tumor-suppressive effects by disrupting the ASC-1 complex to silence NF-κB, highlighting its therapeutic potential via cationic liposomes for treating SNORD50A/B-deficient tumors.