WTAP ‐Mediated m6A Modification of TXNDC5 mRNA Promotes Cervical Carcinogenesis

ABSTRACT

WT1‐associated protein (WTAP), a core component of the methyltransferase complex, is involved in various tumor pathological processes, but its specific mechanism in cervical cancer (CC) remains unclear. This study, based on single‐cell transcriptomic data (including 3 CC and 2 normal tissues), constructed a CC microenvironment cell atlas through unsupervised clustering and identified a novel malignant subpopulation, TXNDC5 ⁺ epithelial cells (TXNDC5 ⁺ EPCs). This epithelial subpopulation was specifically enriched in cancerous tissues compared to normal tissues. Furthermore, within the TXNDC5 ⁺ EPC subpopulation, WTAP and TXNDC5 were co‐expressed. In vitro experiments demonstrated that knocking down WTAP reduced the m6A modification level, mRNA stability, and expression of TXNDC5. RIP experiments confirmed their direct binding. In CCK‐8, colony formation, Transwell assays, flow cytometry, and Western Blot analysis, WTAP knockdown inhibited cell proliferation/migration and accelerated apoptosis, while TXNDC5 overexpression reversed these effects. This study is the first to elucidate that the TXNDC5 ⁺ EPC subpopulation is a dominant malignant driver in CC, regulated by WTAP‐mediated m6A post‐transcriptional modification. Targeting the WTAP‐TXNDC5 axis holds promise as a novel therapeutic strategy for CC, directing a new pathway for clinical intervention.