METTL3's role in cervical cancer development through m⁶A modification

Area of Science:

• Oncology
• Molecular Biology
• Epigenetics

Background:

• N6-methylated adenosine (m⁶A) is a key RNA modification implicated in various cancers.
• The specific role of m⁶A and its regulators in cervical cancer (CC) remains largely undefined.

Purpose of the Study:

• To investigate the function and mechanism of methyltransferase-like 3 (METTL3) in cervical cancer.
• To identify downstream targets and signaling pathways influenced by METTL3 in CC.

Main Methods:

• Assessed METTL3 expression using western blotting, qPCR, and immunohistochemistry.
• Utilized in vitro and in vivo models to study METTL3's role in CC.
• Employed RNA sequencing, MeRIP-seq, qPCR, and RIP-qPCR to elucidate the molecular mechanism.

Main Results:

• METTL3 expression was significantly upregulated in CC tissues and cell lines.
• METTL3 knockdown suppressed CC cell proliferation and metastasis by inhibiting the AKT/mTOR signaling pathway.
• METTL3-mediated m⁶A modification targeted phosphodiesterase 3A (PDE3A) mRNA, facilitated by YTH domain family protein 3 (YTHDF3).

Conclusions:

• METTL3 acts as an oncogene in cervical cancer, promoting tumor progression through the AKT/mTOR pathway.
• The METTL3/YTHDF3/PDE3A axis represents a novel m⁶A-driven regulatory pathway in CC.
• This axis presents a promising therapeutic target for cervical cancer treatment.