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

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.