Scholarlink

Objective <p>This study explores the molecular mechanism by which lncRNA NEAT1 modulates the expression of the transcription factor CEBPA through competitive binding with miR-195-5p, thereby influencing multiple myeloma (MM) cell autophagy and apoptosis.</p> Methods <p>NEAT1 knockdown was achieved using small interfering RNA (siRNA), while miRNA mimics/inhibitors were introduced into MM cells. Molecular expression levels were analyzed using qRT-PCR and Western blot. Targeting relationships were validated using dual-luciferase reporter assays. Additionally, functional assays assessed alterations in cellular responses. Moreover, a nude mouse subcutaneous xenograft model was used to evaluate intervention effects in vivo.</p> Results <p>NEAT1 knockdown suppressed proliferation and invasion while inducing apoptosis in MM cells, accompanied by impaired autophagic flux. Mechanistically, NEAT1 was competitively bound to miR-195-5p, thereby alleviating its transcriptional repression of CEBPA and subsequently enhancing CEBPA mRNA stability and upregulating protein expression. miR-195-5p overexpression replicated NEAT1 knockdown effects, whereas CEBPA silencing completely abrogated miR-195-5p’s antitumor activity. In vivo experiments further demonstrated that NEAT1 silencing reduced tumor volume, and the administration of miR-195-5p agonists decreased tumor mass. CEBPA protein expression in tumor tissue dropped by 41.6%, with concomitant reductions in the autophagic markers LC3-II and Beclin-1.</p> Conclusion <p>NEAT1 functions as a ceRNA to derepress miR-195-5p, alleviating its suppression of CEBPA. This, in turn, synergistically blocks autophagy flux and activates apoptosis, significantly inhibiting MM progression.</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

LncRNA NEAT1 modulates myeloma cell autophagy and apoptosis by competitively binding miR-195-5p to regulate CEBPA

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年11月3日

查看全文
  • Ting Wang,
  • Hongyue Xu,
  • Wei Tao,
  • Bin Bai,
  • Xiuhui Chen,
  • Bingyun Zhang,
  • Yingchao Liu,
  • Xueyong Zhang

摘要

Objective

This study explores the molecular mechanism by which lncRNA NEAT1 modulates the expression of the transcription factor CEBPA through competitive binding with miR-195-5p, thereby influencing multiple myeloma (MM) cell autophagy and apoptosis.

Methods

NEAT1 knockdown was achieved using small interfering RNA (siRNA), while miRNA mimics/inhibitors were introduced into MM cells. Molecular expression levels were analyzed using qRT-PCR and Western blot. Targeting relationships were validated using dual-luciferase reporter assays. Additionally, functional assays assessed alterations in cellular responses. Moreover, a nude mouse subcutaneous xenograft model was used to evaluate intervention effects in vivo.

Results

NEAT1 knockdown suppressed proliferation and invasion while inducing apoptosis in MM cells, accompanied by impaired autophagic flux. Mechanistically, NEAT1 was competitively bound to miR-195-5p, thereby alleviating its transcriptional repression of CEBPA and subsequently enhancing CEBPA mRNA stability and upregulating protein expression. miR-195-5p overexpression replicated NEAT1 knockdown effects, whereas CEBPA silencing completely abrogated miR-195-5p’s antitumor activity. In vivo experiments further demonstrated that NEAT1 silencing reduced tumor volume, and the administration of miR-195-5p agonists decreased tumor mass. CEBPA protein expression in tumor tissue dropped by 41.6%, with concomitant reductions in the autophagic markers LC3-II and Beclin-1.

Conclusion

NEAT1 functions as a ceRNA to derepress miR-195-5p, alleviating its suppression of CEBPA. This, in turn, synergistically blocks autophagy flux and activates apoptosis, significantly inhibiting MM progression.