The long noncoding RNA HOTAIR serves as a microRNA-34a-5p sponge to reduce nucleus pulposus cell apoptosis via a NOTCH1-mediated mechanism

Intervertebral disc degeneration (IDD) is a major cause of lower back pain, but the specific molecular mechanisms governing its development are poorly characterized. This study sought to assess to what extent HOTAIR, a long non-coding (Lnc) RNA is expressed in IDD and regulates the apoptotic death of nucleus pulposus (NP) cells. We therefore used real-time qPCR to measure HOTAIR and microRNA(miR)-34a-5p in degenerative NP cells, and then validated their functional relevance via overexpressing them in these NP cells. We further verified the targets of these RNA constructs in 293 T cells through the use of a dual luciferase reporter assay. We further measured NP cell apoptosis via flow cytometry and Notch1 expression via western blotting. Our results indicated that IDD was linked with decreased HOTAIR expression relative to regular NP cells, and overexpressing this lncRNA was linked to reduced apoptotic NP cell death, whereas overexpressing miR-34a-5p had the opposite effect. We found that HOTAIR served as a miR-34a-5p sponge, sequestering this miRNA and thereby down regulating genes linked to apoptosis through the Notch signaling pathway. Even in naturally degenerated NP cells, HOTAIR delayed the onset of apoptosis. Together these results reveal that a HOTAIR/miR-34a-5p/Notch1 signaling pathway may regulate the development of IDD, potentially making HOTAIR a viable target for treatment of this disease. •The present study proved that miRNA-34a-5p promotes NP cell apoptosis via targeting Notch1 for degradation.•Long non-coding RNA HOX transcript antisense RNA (LncRNA HOTAIR) can serve as a miR-34a-5p sponge, thereby overcoming its ability to promote apoptosis.•HOTAIR overexpression can decrease rates of apoptosis in healthy and naturally degenerative nucleus pulposus cells, while the current study only focus on degenerative NP cells induced by apoptosis factors.•We firstly demonstrate LncRNAs differential effects in NP cells of different pfirrmann grades, optimal improvement was showed in grade IV cells, which may suggest the best time window for IDD gene therapy.