The role of the LncRNA XIST/miR-15a-5p/ MN1signaling axis in gender disparities in bladder cancer prognosis

Through comprehensive analysis of the GSE13507 and The Cancer Genome Atlas (TCGA) cohorts, we identified the X chromosome gene long non-coding RNA (LncRNA) X-inactive specific transcript (XIST) as a critical factor in BC sex disparity. Increased XIST mRNA levels were significantly associated with dismal overall survival in female BC patients. Functional assays demonstrated that XIST promotes tumor cell proliferation, migration, and invasion of BC cells in vitro and in vivo. Further investigation revealed that XIST exerts these activities via the miR-15a-5p/meningioma 1 (MN1) signaling axis, which in turn upregulates frizzled class receptor 2 (FZD2) expression. Notably, FZD2 is an important receptor in the Wnt/β-catenin signaling pathway, overexpressed in BC and various malignant tumors. BC patient specimen analysis revealed that XIST and MN1 were significantly upregulated in BC tissues, with a higher fold increase in females. Conversely, miR-15a-5p expression was downregulated in BC tissues, with a greater fold decrease observed in females.Conclusions：The XIST/miR-15a-5p/MN1/FZD2 signaling axis emerges as a key contributor to gender disparities in bladder cancer prognosis. XIST represents a potential therapeutic target, particularly for female patients.