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December 8, 2025Blood

KPNA2 enhances autophagy through activation of the non-canonical NF-κB signaling pathway, thereby promoting the induction of bortezomib resistance in multiple myeloma

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Authors

HWHuan WangFLFei Li

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Overview

Analysis shows KPNA2 enhances drug resistance and invasion in multiple myeloma, implying novel therapeutic targets may improve treatment outcomes.

Key Points

  • The study aimed to investigate the role of KPNA2 in promoting bortezomib resistance via autophagy in multiple myeloma.
  • Transcriptional profiling of KPNA2 in plasma cells using GEO datasets
  • Generated MM models with shRNA-mediated KPNA2 knockdown and KPNA2 overexpression
  • Evaluated proliferation, invasion, migration, and autophagic flux in MM cells
  • Performed RNA sequencing to identify dysregulated pathways
  • Established murine xenograft model to study tumor dynamics and BTZ resistance
  • KPNA2 expression was significantly higher in newly diagnosed MM patients compared to healthy donors
  • KPNA2 knockdown reduced cellular proliferation, invasion, and migration in vitro and in vivo models
  • KPNA2 overexpression resulted in increased BTZ resistance
  • Silencing KPNA2 combined with BTZ enhanced cytotoxicity and apoptosis induction
  • Transcriptomic profiling revealed enrichment of autophagy-related pathways following KPNA2 depletion

Cite This Study

Wang et al. (2025) studied this question.

synapsesocial.com/papers/69362f3d4fa91c937236d4bfhttps://doi.org/10.1182/blood-2025-7478
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