Integrated molecular subtyping and functional analysis of circ_0001946/miR-7-5p axis reveals a glucose metabolism-linked regulatory mechanism in ovarian cancer
Ovarian cancer (OvCa) remains one of the most lethal gynecological malignancies, primarily due to late-stage diagnosis, chemoresistance, and substantial molecular heterogeneity. Emerging evidence highlights the pivotal roles of microRNAs (miRNAs) and circular RNAs (circRNAs) in tumor progression. Among them, miR-7-5p has been implicated in tumor suppression and the regulation of metabolic pathways. However, its functional interaction with circ_0001946 in OvCa has yet to be elucidated. This study aimed to investigate the interplay between miR-7-5p and circ_0001946 in OvCa, with a particular focus on their regulatory roles in apoptosis, proliferation, tumorigenesis, and glucose metabolism. Using integrated bioinformatics analyses of TCGA and GEO datasets, we identified glucose metabolism-related molecular subtypes. Functional enrichment, immune landscape profiling, and LASSO regression were employed to validate these subtypes and develop prognostic risk models. A series of in vitro and in vivo experiments-including qPCR, CCK-8 assay, flow cytometry, colony formation, dual-luciferase reporter assay, and xenograft tumor models in nude mice-were conducted to evaluate the expression and functional effects of miR-7-5p and circ_0001946. Two molecular subtypes, Subtype-A and Subtype-B, with distinct glucose metabolism and immune profiles were identified. Subtype-A correlated with advanced-stage disease and chemoresistance, while Subtype-B exhibited better prognosis, higher immune infiltration, and activation of metabolic pathways. Circ_0001946 was upregulated in OvCa tissues and cell lines and acted as an oncogene by sponging miR-7-5p. Functional assays revealed that downregulation of miR-7-5p or overexpression of circ_0001946 promoted cell proliferation, inhibited apoptosis, and accelerated tumor growth. Dual-luciferase reporter assays confirmed a direct interaction between miR-7-5p and circ_0001946. Clinical tissue analysis further showed elevated miR-7-5p expression in para-cancerous tissues. The circ_0001946/miR-7-5p regulatory axis contributes to OvCa progression by suppressing apoptosis and promoting cellular proliferation. Targeting this axis presents a promising therapeutic avenue. Additionally, molecular subtyping based on glucose metabolism-related genes offers valuable prognostic information and supports the advancement of personalized treatment strategies in OvCa.