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.