Related Experiment Video

Updated: Mar 15, 2026

Monitoring eIF4F Assembly by Measuring eIF4E-eIF4G Interaction in Live Cells
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Monitoring eIF4F Assembly by Measuring eIF4E-eIF4G Interaction in Live Cells

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METTL16 enhances proteasome inhibitor resistance in multiple myeloma by inhibiting eIF2α-PERK interaction and

Guanli Wang1, Xuejie Gao1, Hui Zhang1

  • 1Department of Hematology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.

Oncogene
|March 14, 2026
PubMed

Insights

METTL16 regulates multiple myeloma (MM) progression and proteasome inhibitor (PI) resistance through translational control, not RNA methylation. Targeting METTL16 enhances PI efficacy in MM cells.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Proteasome inhibitor (PI) resistance is a significant challenge in multiple myeloma (MM) treatment.
  • Identifying novel therapeutic targets is crucial for overcoming PI resistance.

Purpose of the Study:

  • To investigate the role of METTL16 in multiple myeloma progression and its impact on proteasome inhibitor sensitivity.
  • To explore the underlying mechanisms of METTL16's function in MM.

Main Methods:

  • Investigated METTL16's role in MM cells.
  • Analyzed PERK-eIF2α interaction and eIF2α phosphorylation.
  • Assessed translation of key transcripts (PSMB5, CCND1).
  • Evaluated the effect of pharmacological METTL16 targeting on PI efficacy.

Main Results:

  • METTL16 overexpression correlates with altered PERK-eIF2α interaction and reduced eIF2α phosphorylation.
  • Increased translation of PSMB5 and CCND1 was observed with METTL16 overexpression.
  • METTL16 targeting enhanced the efficacy of proteasome inhibitors in MM cells.
  • METTL16 functions independently of its m6A methyltransferase activity.

Conclusions:

  • METTL16 acts as a regulator of MM progression and PI sensitivity via translational control.
  • METTL16 represents a potential therapeutic target for enhancing proteasome inhibitor-based therapy in multiple myeloma.

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