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Long non-coding RNA FEZF1-AS1 suppresses ferroptosis in multiple myeloma cells through KIAA1429-mediated m6A

Qing Su1, Weiliang Liu2, Peijin Wang3

  • 1Department of Bone Oncology, Yantai Shan Hospital, Yantai, 264001, China.

Human Cell
|October 14, 2025
PubMed

Insights

Long non-coding RNA FEZF1-AS1 promotes multiple myeloma cell survival by inhibiting ferroptosis. This occurs via a pathway involving KIAA1429-mediated m6A modification of OTUB1, which stabilizes SLC7A11 expression.

Area of Science:

  • Hematologic Malignancies
  • Molecular Biology
  • Cancer Research

Background:

  • Multiple myeloma (MM) is a cancer of plasma cells.
  • Understanding the molecular mechanisms driving MM progression is crucial for developing new therapies.
  • Ferroptosis, a regulated form of cell death, is implicated in cancer, but its role in MM requires further elucidation.

Purpose of the Study:

  • To investigate the role of the long non-coding RNA FEZF1-AS1 in regulating ferroptosis in multiple myeloma cells.
  • To elucidate the molecular mechanism involving KIAA1429-mediated N6-methyladenosine (m6A) modification and OTUB1 in this process.
  • To identify potential therapeutic targets for MM.

Main Methods:

  • Quantitative real-time PCR and Western blot analysis to assess gene and protein expression.
  • Cell viability assays, reactive oxygen species (ROS) detection, and assessment of ferroptosis markers (GSH, Fe2+, MDA, SLC7A11, GPX4, ACSL4).
  • RNA pull-down, RNA immunoprecipitation (RIP), and co-immunoprecipitation assays to validate molecular interactions and modifications.

Main Results:

  • FEZF1-AS1, KIAA1429, and OTUB1 were highly expressed in MM cells.
  • FEZF1-AS1 knockdown reduced MM cell viability and induced ferroptosis.
  • FEZF1-AS1 stabilizes KIAA1429 mRNA via IGF2BP3; KIAA1429 promotes m6A modification of OTUB1 mRNA, increasing its stability and expression; OTUB1 deubiquitinates and stabilizes SLC7A11, inhibiting ferroptosis.

Conclusions:

  • FEZF1-AS1 promotes MM cell survival by suppressing ferroptosis through the KIAA1429/m6A/OTUB1/SLC7A11 axis.
  • Targeting FEZF1-AS1 or its downstream effectors may represent a novel therapeutic strategy for multiple myeloma.
Keywords:
FerroptosisKIAA1429LncRNA FEZF1-AS1Multiple myelomaOTUB1

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