Identification of a functional CircRNA-miRNA-mRNA network and inhibitory effect of Hsa_circ_0001681 on gliomas

Objective: Gliomas pose a significant global health challenge due to high rates of morbidity and mortality. Recent research has indicated that circular RNAs (circRNAs) may play a crucial role in gliomas. However, the specific impacts of circRNAs on gliomas development is poorly understood. Therefore, the present study aimed to explore the roles of circRNAs in gliomas by analyzing their interactions with microRNAs (miRNAs) and messenger RNAs (mRNAs). Methods: Datasets were extracted from the Gene Expression Omnibus (GEO) database to investigate differentially expressed circRNAs in gliomas. Using the Circular RNA Interactome, we predicted interactions between the identified circRNAs and 125 target miRNAs, focusing on 15 key miRNAs selected by intersection analysis. The miRNet database was applied to predict 2635 target mRNAs, constructing a comprehensive circRNA-miRNAmRNA network, while functional enrichment analyses were conducted to determine the roles of this network. Results: Four circRNAs with significant differential expression in glioma samples were identified. The constructed network indicated the substantial involvement of transcriptional regulation and cancer-related pathways. Notably, hsa_circ_0001681 was highlighted as a key circRNA, which was further validated through Sanger sequencing and quantitative reverse transcription PCR (qRT-PCR). Functional assays, including cellular assays and animal xenograft experiments, demonstrated that hsa_circ_0001681 inhibits glioma carcinogenesis in vitro and in vivo. Conclusion: Our investigation highlights the significant role of the circRNA-miRNA-mRNA network in the pathophysiology of gliomas, and supports the potential of hsa_circ_0001681 as a diagnostic and therapeutic biomarker. These findings present new opportunities for understanding the molecular mechanisms underlying glioma and developing targeted treatments.