Zhu Yang

Activated MAFB in ovarian cancer promotes cytoskeletal remodeling and immune microenvironment suppression by interfering with m6A modifications through WTAP competition

The tumor microenvironment (TME) coordinates cancer progression through complex transcriptional networks, but the molecular mechanisms controlling immune evasion in ovarian cancer remain elusive. Here, by integrating immune dysfunction characteristics across multiple clinical cohorts and single-cell transcriptomics, we identified MAFB as a major regulator of ovarian cancer progression. MAFB expression exhibited stage-dependent elevation and was associated with immune checkpoint characteristics. Mechanistically, MAFB competitively binds to the core component WTAP of the m6A methyltransferase complex, thereby antagonizing the degradation of target gene mRNAs (WNT5A, CD55). This atypical regulatory axis leads to persistent expression of the target genes, further coordinating tumor cell invasiveness and immune landscape remodeling through cytoskeletal protein reorganization, M2 macrophage polarization, and regulatory T cell infiltration. Correlative analyses in patient cohorts and therapeutic effects in preclinical models support the clinical relevance of this pathway. Our findings uncover a novel mechanism by which MAFB promotes ovarian cancer progression through cytoskeletal remodeling and immune suppression, connecting transcriptional regulation with epitranscriptomic modifications, and identify the MAFB-WTAP-CD55 axis as a potential therapeutic target in ovarian cancer.

Ultrasound-Mediated Long-Circulating Nanopolymer Delivery of Therapeutic siRNA and Antisense MicroRNAs Leads to Enhanced Paclitaxel Sensitivity in Epithelial Ovarian Cancer Chemotherapy

Epithelial ovarian cancer (EOC) is one of the leading malignant tumors that seriously threaten women's health. The development of new drugs or increasing the sensitivities of current chemotherapy drugs is critically needed. The purpose of this study was to assess the synergistic effects of two silencing RNAs [salt-inducible kinase 2 (SIK2) siRNA and antisense-microRNA21 (anti-miR21)] encapsulated in long-circulating folate-lipid-poly(lactic-