Circular RNA hsa_circ_0001658 Inhibits Intervertebral Disc Degeneration Development by Regulating hsa-miR-181c-5p/FAS

Abstract

Background and Purpose. Intervertebral disc degeneration (IDD) is the main cause of low back pain, but its pathogenesis has not been studied clearly. Circular RNA is a type of noncoding RNA (ncRNA). In this study, we studied the potential role of circular RNA in the pathogenesis of IDD. Methods. We obtained microarray data (GSE116726, GSE67566) from Gene Expression Omnibus database, and differential expression level of ncRNA in nucleus pulposus (NP) tissues of IDD patients was analyzed. The potential circRNA-miRNA-mRNA regulatory network was analyzed by starBase. The effect of the interaction between hsa_circ_0001658, hsa-miR-181c-5p, and FAS on the proliferation and apoptosis of human neural progenitor cells (hNPCs) was studied. Results. hsa_circ_0001658 was significantly upregulated ( logFC > 2.0 and adj . P . Val < 0.01 ) in the NP tissues of IDD patients, and hsa-miR-181c-5p expression was downregulated ( logFC < − 2.0 and adj . P . Val < 0.01 ). Silencing of hsa-miR-181c-5p or overexpression of hsa_circ_0001658 inhibited the proliferation of hNPCs and promoted their apoptosis. hsa_circ_0001658 acted as a sponge of hsa-miR-181c-5p. hsa-miR-181c-5p downregulated the expression of Fas cell surface death receptor (FAS), promoted the proliferation, and inhibited the apoptosis of hNPCs. hsa_circ_0001658 functioned in hNPCs through targeting hsa-miR-181c-5p/FAS. Conclusion. Circular RNA hsa_circ_0001658 inhibits IDD development by regulating hsa-miR-181c-5p/FAS. It is expected to be a potential target for the therapy of IDD.

Key LncRNAs Associated With Oxidative Stress Were Identified by GEO Database Data and Whole Blood Analysis of Intervertebral Disc Degeneration Patients

“…LINC01359 may be linked to hepatocellular carcinoma (HCC), that's all we got (Tan et al, 2019). LUCAT1 is not available in PubMed, but the silencing of hsa-miR-181c-5p can inhibit the proliferation and promote the apoptosis of nucleus pulposus cells (Meng and Xu, 2021). We revealed a direct association between these four key lncRNAs and IDD, it may be important for the pathogenesis and clinical treatment exploration of IDD, which will be our focus in the future.…”

The pathological mechanisms of circRNAs in mediating intervertebral disc degeneration

“…Apoptosis was the first type of RCD to be identified [ 85 ]. Sixteen circRNAs have been reported to regulate NPCs apoptosis, including nine circRNAs that were shown to promote NPCs apoptosis (circ_0004354 [ 63 ], circ_0040039 [ 63 ], circITCH [ 64 ], circ_0083756 [ 65 ], circRNA_0000253 [ 67 ], circ_001653 [ 69 ], circRNA_104670 [ 70 ], circ_RERE [ 87 ], and circ_0001658 [ 88 ]) and seven circRNAs that were shown to inhibit NPCs apoptosis (circGLCE [ 76 ], circRNA VMA21 [ 77 ], circ- GRB10 [ 78 , 79 ], circRNA-CIDN [ 80 ], circERCC2 [ 81 ], circARL15 [ 89 ], and circ_0059955 [ 90 ]) ( Table 1 and Fig. 2 ).…”

Regulatory roles of noncoding RNAs in intervertebral disc degeneration as potential therapeutic targets (Review)

“…Wang et al ( 88 ) reported that circ_0001658 is significantly upregulated in osteosarcoma tissue and increases proliferation, migration and invasion of osteosarcoma cells and suppresses apoptosis by targeting the miR-382-5p/YB-1 signaling pathway. Meng and Xu ( 89 ) found that circ_0001658 expression is significantly increased in the NP tissue obtained from patients with IDD and hsa-miR-181c-5p is downregulated. In addition, they revealed that circ_0001658 upregulation suppressed proliferation of NP cells and increased apoptosis.…”