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Updated: Jun 11, 2025

Repression of Multiple Myeloma Cell Growth In Vivo by Single-wall Carbon Nanotube SWCNT-delivered MALAT1 Antisense Oligos
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Aberrant NSUN2-mediated m5C modification of exosomal LncRNA MALAT1 induced RANKL-mediated bone destruction in

Manya Yu1, Zhiguo Cai2, Jie Zhang3

  • 1The First School of Clinical Medicine, Shandong University of Traditional Chinese Medicine, No. 16369 Jingshi Road, Jinan, 250014, China.

Communications Biology
|October 2, 2024
PubMed

Insights

Exosomes from multiple myeloma cells transfer MALAT1 to osteoclasts, promoting bone lesions. This transfer is mediated by NSUN2 and YBX1, highlighting a novel therapeutic target for bone destruction in multiple myeloma.

Area of Science:

  • Molecular Biology
  • Oncology
  • Bone Biology

Background:

  • The role of exosome-mediated communication between multiple myeloma (MM) cells and osteoclasts (OCs) in the development of bone lesions is not fully understood.
  • Understanding the molecular mechanisms driving MM-induced bone destruction is crucial for developing effective treatments.

Purpose of the Study:

  • To investigate the impact of exosome-mediated crosstalk between MM cells and OCs on bone lesions.
  • To elucidate the molecular players and mechanisms involved in MM cell-induced osteoclastogenesis and bone destruction.

Main Methods:

  • Exosome cargo analysis using RNA-sequencing.
  • In vitro osteoclastogenesis assays (TRAP staining, Western blot).
  • In vivo bone destruction assessment (Micro-CT, bone histomorphometry).
  • Molecular interaction studies (RNA pull-down, RIP, MeRIP, luciferase reporter assays).
  • Clinical data analysis of MALAT1, NSUN2, and YBX1 expression.

Main Results:

  • NSUN2 and YBX1-mediated m5C modifications upregulated LncRNA MALAT1 in MM cells, which was transported to OCs via exosomes.
  • Exosomal MALAT1 promoted osteoclast differentiation and bone destruction by enhancing RANKL expression and activating AKT/MAPKs signaling pathways via a ceRNA mechanism.
  • NSUN2 methyltransferase stabilized MALAT1 through the YBX1 reader protein.
  • Clinical data showed a positive correlation between MALAT1, NSUN2, YBX1 levels, bone destruction, and RANKL expression.

Conclusions:

  • Exosomal MALAT1, regulated by NSUN2 and YBX1, plays a critical role in promoting osteoclastogenesis and bone lesions in multiple myeloma.
  • The NSUN2/MALAT1/YBX1 axis represents a potential therapeutic target for mitigating bone destruction in MM patients.

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