ArticleWorld journal of surgical oncology2025
Integrated molecular subtyping and functional analysis of circ_0001946/miR-7-5p axis reveals a glucose metabolism-linked regulatory mechanism in ovarian cancer.
Article in World journal of surgical oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundOvarian 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.
objectiveThis 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.
methodsUsing 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.
resultsTwo 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.
conclusionsThe 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.
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