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Repression of Multiple Myeloma Cell Growth In Vivo by Single-wall Carbon Nanotube SWCNT-delivered MALAT1 Antisense Oligos
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Inhibition of CDC27 O-GlcNAcylation coordinates the antitumor efficacy in multiple myeloma through the

Hai-Qi Wu1, Ren-Cai Qin1, Wei-Jie Li1

  • 1Shenzhen Key Laboratory for Systems Medicine in Inflammatory Diseases, Centre for Infection and Immunity Studies (CIIS), School of Medicine, Shenzhen Campus of Sun Yat-sen University, Shenzhen, 518107, China.

Acta Pharmacologica Sinica
|February 21, 2025
PubMed

Insights

Novel research identifies O-GlcNAcylation transferase (OGT) and cell division cycle 27 (CDC27) as key prognostic genes in multiple myeloma (MM). O-GlcNAcylation regulates CDC27 stability, offering a new therapeutic strategy for MM treatment.

Area of Science:

  • Hematologic Malignancy Research
  • Cancer Genomics
  • Molecular Biology

Background:

  • Multiple myeloma (MM) is a plasma cell malignancy known for aggressive behavior and drug resistance.
  • Identifying novel prognostic genes is crucial for developing effective MM treatments.
  • Current therapeutic strategies require enhancement due to MM cell resistance.

Purpose of the Study:

  • To identify key prognostic genes in multiple myeloma using machine learning on RNA microarray data.
  • To investigate the functional relationship between O-GlcNAcylation transferase (OGT) and cell division cycle 27 (CDC27) in MM.
  • To explore the potential of targeting O-GlcNAcylation and CDC27 stability for MM therapy.

Main Methods:

  • Machine learning analysis of RNA microarray data from 957 MM patients across five cohorts.
  • Gene knockdown (siOGT) and pharmacological modulation of O-GlcNAcylation (OSMI-1, Thiamet G).
  • Mass spectrometry and immunoprecipitation to identify protein targets and interactions.
  • In vitro and in vivo studies to assess combined therapeutic efficacy.

Main Results:

  • O-GlcNAcylation transferase (OGT) and cell division cycle 27 (CDC27) identified as key prognostic genes in MM.
  • O-GlcNAcylation was found to maintain CDC27 protein stability by inhibiting the autophagy-lysosome pathway (ALP).
  • OSMI-1 treatment showed potential to downregulate O-GlcNAcylated CDC27 in MM.1S cells.
  • Combined OSMI-1 and bortezomib (BTZ) demonstrated enhanced antitumor efficacy in MM models.

Conclusions:

  • O-GlcNAcylation plays a novel role in regulating CDC27 protein stability via the autophagy-lysosome pathway in MM.
  • Targeting O-GlcNAcylation represents a potential therapeutic strategy for multiple myeloma.
  • The combination of OSMI-1 and bortezomib shows promise for enhanced MM treatment.
Keywords:
CDC27O-GlcNAcylationbortezomibmachine learningmultiple myeloma

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