Long non-coding RNA RP11-81H3.2 suppresses apoptosis by targeting microRNA-1539/COL2A1 in human nucleus pulposus cells.

Abstract

Intervertebral disk degeneration (IDD) is a severe health problem that results in lower back pain and disability. Previous evidence has indicated that excessive apoptosis of nucleus pulposus (NP) cell is involved in the occurrence and development of IDD. However, the underlying mechanisms regulating NP cell apoptosis are unclear. The present study aimed to investigate the function of a novel long non-coding RNA RP11-81H3.2 in modulating NP cell apoptosis and the potential underlying mechanisms. The results demonstrated that the RP11-81H3.2 expression levels were significantly decreased in NP tissues from patients with IDD compared with those from healthy controls, and that lower expression levels were associated with higher-grade disk degeneration. Functionally, RP11-81H3.2 silencing promoted apoptosis and decreased the viability of NP cells derived from tissue samples of patients with IDD, whereas RP11-81H3.2 overexpression induced opposite effects. Bioinformatics analysis, luciferase assays and reverse transcription-quantitative PCR revealed that microRNA (miR)-1539 was a direct target of RP11-81H3.2. A mechanistic analysis demonstrated that RP11-81H3.2 functioned as an RNA sink to downregulate miR-1539, which led to the upregulation of collagen type 2 α 1 chain (COL2A1), a target of miR-1539. Collectively, the present results suggested that lower RP11-81H3.2 expression levels were associated with higher-grade IDD, and that RP11-81H3.2 inhibited NP cell apoptosis by decreasing the levels of miR-1539 to increase COL2A1 expression levels. The present study identified a beneficial role of RP11-81H3.2 against NP cell apoptosis.