Work

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

Year: 2025

Type: article

Abstract: 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.

Source: Discover Oncology

DOI: 10.1007/s12672-025-03869-2