CircRNA expression profile and potential role of hsa_circ_0040039 in intervertebral disc degeneration.

PURPOSE: Circular RNAs (circRNAs) play an critical role in the pathological processes associated with IDD. However, the potential roles of circRNAs in IDD remain largely unclear. Here, we identify the circRNAs expression profiles and elucidate the potential role of candidate circRNAs in the pathogenesis of intervertebral disc degeneration (IDD) through microarray data and bioinformatics analyses. METHODS: We obtained the datasets of microarrays (GSE67566 and GSE116726) from the Gene Expression Omnibus database. The differentially expressed circRNAs and miRNAs were identified using the Limma R package. The target miRNAs and target genes of the candidate circRNAs were predicted using an online tool. Functional enrichment analyses of the target genes were performed using the clusterProfiler R package. A protein-protein interaction (PPI) network was constructed using STRING. RESULTS: A total of 104 differentially expressed circRNAs were identified between the IDD and the control groups, including 41 upregulated circRNAs and 63 downregulated circRNAs (cutoff criteria (|log2 fold change| > 2, P < .05)). Hsa_circ_0040039, which was the most upregulated circRNA (log2 fold change = 2.95), was selected for further analysis. The regulatory circRNA-miRNA-mRNA network comprised hsa_circ_0040039, 2 target miRNAs (hsa-miR-424-5p and hsa-miR-15b-5p), and 77 target genes. Functional enrichment analysis showed that the 77 promising target genes are mainly enriched in the ubiquitin proteasome system and Wnt signaling pathway. Further, the PPI network showed that the top 3 hub genes are BRTC, SIAH1, and UBE2V1. CONCLUSIONS: A total of 104 differentially expressed circRNAs were identified between the IDD and control groups. Hsa_circ_0040039 may serve as a sponge of hsa-miR-424-5p and hsa-miR-15b-5p, to regulate the expression of downstream genes (such as BRTC, SIAH1, and UBE2V1); thus, it may be involved in IDD-associated pathological processes via the Wnt/ß-catenin signaling pathway. Further studies are required to confirm the potential roles of hsa_circ_0040039 in IDD.

CSN5 controls the growth of osteosarcoma via modulating the EGFR/PI3K/Akt axis.

CSN5, a critical subunit of the constitutive photomorphogenesis 9 (COP9) signalosome (CSN), functions as a potential tumor promoter in various cancers. However, the biological functions and clinical significance of CSN5 in osteosarcoma (OS) remains unclear. Here, we report that OS tumors overexpressed CSN5 compared with normal bone tissues, and CSN5 overexpression was obviously associated with the malignant phenotype and poor prognosis in patients with OS. In addition, high CSN5 expression significantly promoted the growth of OS cells, whereas CSN5 silence suppressed the tumorigenicity of OS cells. Furthermore, we found PI3K/Akt signaling pathway contributed to the effects of CSN5 in OS cells, and blocking the Akt pathway significantly inhibited the actions of CSN5. Mechanistically, we demonstrate that CSN5 positively regulated EGFR stability through reducing the levels of EGFR ubiquitination, thereby activating the PI3K/Akt signaling pathway in OS cells. Moreover, our results shown that the oncogenic effects of CSN5 on OS cells were EGFR dependent. Thus, CSN5 has a central role in regulating diverse aspects of the pathogenesis of OS, which could be a potential diagnostic and therapeutic target for OS.