Hsa-circ-0064636 regulation of the target gene VDAC1/UBE4A by hsa-miR-326/hsa-miR-503-5 in osteosarcoma

Abstract Background: Circular RNAs (circRNAs) are a subclass of non-coding RNAs that play a critical role in regulating gene expression in eukaryotic organisms. Recent studies have revealed the critical role of circRNAs in cancer progression. However, there are few studies on the function of hsa-circ-0064636 in osteosarcoma (OS).Methods: The differential expression of hsa-circ-0064636 in OS cell lines was detected by [1] quantitative real-time PCR (qRT-PCR). Differentially expressed mRNAs and miRNAs were screened in OS mRNA and miRNA expression datasets. MiRNAs that interacted with hsa-circ-0064636 were predicted by RNAhybrid, TargetScan and miRanda, and were further detected using RNAhybrid, TargetScan and miRanda. MiRWalk, miRMap, and miRNAMap were used to perform target gene prediction on the intersected miRNAs to construct a circ-miRNA-mRNA interactor network. The target genes were then subjected to survival analysis using PROGgeneV2, and then a circ-miRNA-mRNA interaction subnetwork was formed, and the prognostic impact of target genes was revealed.[2] Results: The qRT-PCR experiments showed that hsa-circ-0064636 was significantly overexpressed in the OS cell lines. Hsa-mir-326(miR-326) and hsa-mir-503-5p(miR-503-5p) are targeting miRNAs of hsa-circ-0064636 in the target genes obtained from the miR-326 and miR-503-5p screens. UBE4A and VDAC1 have a significant effect on prognosis. UBE4A is a target gene of miR-326, while VDAC1 is a target gene of miR-503-5p.Conclusion: Hsa-circ-0064636 may be involved in OS development by inhibiting the expression of miR-326 and miR-503-5p, thus regulating that of VDAC1 and UBE4A.