Identification of a Functional circRNA-miRNA-mRNA Network and Inhibitory Effect of Hsa_circ_0001681 on Gliomas

Abstract

Abstract Background Gliomas seriously threaten the health and safety of patients globally with significant morbidity and mortality. An increasing number of studies have confirmed the close correlation between circular RNAs (circRNAs) and the occurrence and development of cancer. However, the association between circRNAs and their downstream networks with gliomas remains unclear. Results Our study identified 4 significantly differentially expressed circRNAs through the glioma expression profile from the Gene Expression Omnibus database. A total of 125 circRNA-targeted microRNAs (miRNAs) were predicted using the Circular RNA Interactome database, 15 of which were selected for further mining from intersection analysis. A total of 2635 miRNA-targeted mRNAs were predicted using the miRNet database, thus establishing the circRNA-miRNA-mRNA network. Functional enrichment pathway analyses revealed that the mRNAs contained in the network were enriched in a variety of DNA- or RNA-related transcription regulatory processes and pathways in cancer. Hsa_circ_0001681 was further identified as a hub circRNA and validated by Sanger sequencing and RT-PCR. Cell biology experiments and xenograft models revealed that hsa_circ_0001681 played an anticarcinogenic role in gliomas both in vitro and in vivo. Conclusions Our results identified and indicated the crucial role of circRNA-miRNA-mRNA network in gliomas and supported the potential of hsa_circ_0001681 as a diagnostic and therapeutic target biomarker.