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

objectiveThis 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.

methodsNEAT1 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.

resultsNEAT1 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.

conclusionNEAT1 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.