WTAP-Mediated m6A Modification of TXNDC5 mRNA Promotes Cervical Carcinogenesis

Area of Science:

• Oncology
• Molecular Biology
• Genomics

Background:

• WT1-associated protein (WTAP) is implicated in tumor progression, but its role in cervical cancer (CC) is not fully understood.
• WTAP is a key component of the m6A methyltransferase complex, influencing gene expression post-transcriptionally.

Purpose of the Study:

• To investigate the mechanism of WTAP in cervical cancer progression using single-cell transcriptomic data.
• To identify novel malignant cell subpopulations and their regulatory pathways in the CC microenvironment.

Main Methods:

• Single-cell RNA sequencing of CC and normal tissues to construct a cell atlas.
• Unsupervised clustering to identify cell subpopulations, including TXNDC5+ epithelial cells (TXNDC5+EPCs).
• In vitro experiments (WTAP knockdown, TXNDC5 overexpression, RIP, CCK-8, colony formation, Transwell, flow cytometry, Western Blot) to validate findings.

Main Results:

• A novel malignant subpopulation, TXNDC5+EPCs, was identified and enriched in CC tissues.
• WTAP and TXNDC5 were co-expressed in TXNDC5+EPCs, with WTAP regulating TXNDC5 expression and stability via m6A modification.
• WTAP knockdown inhibited CC cell proliferation and migration while promoting apoptosis; TXNDC5 overexpression reversed these effects.

Conclusions:

• The TXNDC5+EPC subpopulation is a major driver of cervical cancer malignancy, regulated by WTAP-mediated m6A modification.
• The WTAP-TXNDC5 axis represents a promising therapeutic target for cervical cancer intervention.