Extracellular matrix (ECM) remodeling promotes prostate cancer progression, while the prognostic value and cellular context of ECM-related genes (ERGs) remain unclear. A 4-gene ERG signature for disease-free interval prediction was built using TCGA-PRAD data, and the hub gene Fibromodulin (FMOD) was validated in an external cohort via scRNA-seq, bulk deconvolution and siRNA knockdown. The signature stratified patient prognosis, and FMOD exerted the strongest protective effect. Despite higher bulk expression in tumor tissues, FMOD predicted better clinical outcomes. FMOD was enriched in a low-chromosomal-instability, low-proliferation epithelial subpopulation with enhanced stromal-immune crosstalk, and FMOD knockdown boosted cancer cell proliferation and colony formation. FMOD identifies a low-malignancy epithelial state linked to favorable prostate cancer prognosis, supporting cell state-resolved validation of ECM-related prognostic biomarkers.
The ion channel gene GJB2 emerges as a therapeutic target for LUAD with significant prognostic value. Herein, the potential mechanisms of GJB2 were investigated. GJB2 expression was analyzed by bioinformatics, RT-qPCR and western blotting. In vitro functional assays and A549 xenografts detected the role of GJB2. The upstream mechanism of GJB2 was explored. GJB2 was up-regulated and associated with the poor overall survival of LUAD patients. GJB2 knockdown inhibited cell malignancy and impaired mitochondrial homeostasis. HSF4 enhanced GJB2 transcription. GJB2 knockdown lowered PI3K/AKT activity. SC79 reversed the in vitro impacts of GJB2 inadequacy and promoted tumor growth when HSF4 was up-regulated and GJB2 was down-regulated simultaneously. GJB2, transcriptionally activated by HSF4, activates PI3K/AKT pathway to support LUAD tumorigenesis and development.
Glioblastomas (GBs) are the most frequent and aggressive central nervous system tumors, whose progression is influenced by sex hormones. 17β-estradiol (E2), promotes an epithelial-to-mesenchymal transition (EMT)-like process and enhances proliferative, migratory, and invasive capacities in GB through intracellular estrogen receptors. However, the role of G protein-coupled estrogen receptor (GPER) in GB remains poorly understood. We evaluated the effects of E2, the GPER-agonist G-1, and the GPER-antagonist G-15 on EMT-related processes, migration, and invasion in U251 and U87 GB-derived cells. GPER activation by E2 and G-1 increased migration and invasion, whereas G-15, alone or combined, reduced these effects. GPER activation also induced a mesenchymal-like phenotype. These findings suggest that GPER-associated signaling contributes to EMT-like phenotypic changes, migration, and invasion in GB.
This cross-sectional study investigated galectin-1, -3, and -9 in adenomyosis. Analysis of hysterectomy tissues from premenopausal women via western blot, qPCR, immunohistochemistry, and Masson's staining revealed significantly elevated galectin levels compared to controls. Galectin expression positively correlated with fibrosis severity (r = 0.476, 0.925, 0.563, all p < .05), which in turn moderately correlated with dysmenorrhea (VAS score) and uterine enlargement. Findings indicate that galectins are implicated in adenomyosis-related fibrosis and pain, suggesting their potential as therapeutic targets.
Endometrial cancer(EC) is increasing worldwide, but its molecular mechanisms remain unclear. This study explored whether RBM15B-mediated m6A modification of FOXM1 promotes EC progression through the AURKA/TPX2 axis and epithelial-mesenchymal transition(EMT). Bioinformatics analyses assessed FOXM1 expression and prognosis in EC. RNA pull-down, MeRIP-PCR, dot blot, and RNA stability assays examined m6A regulation. Colony formation, Transwell, wound healing, and tumor sphere assays evaluated malignant behaviors. FOXM1 was significantly upregulated in EC and associated with unfavorable prognosis. Functional assays showed that FOXM1 enhanced proliferation, migration, invasion, and stemness of EC cells. Mechanistically, RBM15B increased m6A modification of FOXM1 mRNA and promoted expression. RBM15B knockdown inhibited malignant phenotypes and reduced activation of the downstream AURKA/TPX2 pathway. RBM15B-mediated m6A methylation stabilizes FOXM1 expression, activates the AURKA/TPX2 axis, and promotes EMT and EC progression. Targeting the RBM15B/FOXM1/AURKA/TPX2 pathway may offer therapeutic potential.
