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The METTL3-IGF2BP3 axis drives osteosarcoma progression by enhancing ID1 mRNA stability

Rongbing Shu1, Qiuxin Cheng1, Zhuanyi Yu1

  • 1Department of Orthopedics, Yingtan People's Hospital, No. 1, Longhushan North Avenue, Yingtan, Jiangxi Province, 335000, China.

BMC Musculoskeletal Disorders
|January 30, 2026
PubMed
Abstract

Insights

The METTL3-IGF2BP3 axis promotes osteosarcoma (OS) progression by stabilizing ID1 mRNA through N6-methyladenosine (m6A) modification. This axis enhances OS cell proliferation, migration, invasion, and tumor growth, presenting a potential therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Epigenetics

Background:

  • Osteosarcoma (OS) is an aggressive bone cancer with poorly understood progression mechanisms.
  • ID1 is a known factor in OS progression, but its regulatory pathways require elucidation.

Purpose of the Study:

  • To investigate the role of the METTL3-IGF2BP3 axis in regulating ID1 mRNA stability and its functional impact on osteosarcoma.
  • To explore the underlying N6-methyladenosine (m6A) modification mechanisms.

Main Methods:

  • Bioinformatic analysis (ENCORI, RM2Target) and machine learning to identify core regulators.
  • In vitro assays (CCK-8, colony formation, wound healing, Transwell) to assess cell behavior.
  • In vivo xenograft mouse model to evaluate tumor growth.
  • Molecular techniques including MeRIP-qPCR, RIP-qPCR, and RNA stability assays.

Main Results:

  • METTL3 and IGF2BP3 were identified as core regulators of ID1, with elevated expression in OS.
  • METTL3-mediated m6A modification of ID1 mRNA enhanced IGF2BP3 binding, stabilizing ID1 transcripts.
  • The METTL3-IGF2BP3 axis promoted OS cell proliferation, migration, and invasion.
  • In vivo studies confirmed accelerated tumor growth driven by this axis.

Conclusions:

  • The METTL3-IGF2BP3 axis promotes osteosarcoma progression via m6A-dependent stabilization of ID1 mRNA.
  • This axis represents a promising therapeutic target for osteosarcoma treatment.
Keywords:
ID1IGF2BP3METTL3Osteosarcomam6AmRNA stability

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