Intervertebral disc degeneration (IDD) is a chronic skeletal muscle degeneration disease. Previous studies have demonstrated that long non-coding RNAs (lncRNAs) exert significant roles in serious illnesses. Prostate androgen-regulated transcript 1 (PART1) is an identified lncRNA that has been reported to be a regulator in a number of diseases. However, the potential effects of PART1 in IDD have yet to be fully elucidated. The present study aimed to investigate the roles of lncRNA PART1 in IDD and identify a possible underlying mechanism. Human nucleus pulposus (NP) cells were first exposed to lipopolysaccharide (LPS) to construct in vitro IDD models. Reverse transcription-quantitative PCR (RT-qPCR) was performed to measure lncRNA PART1 expression levels in 10 ng/ml LPS-stimulated NP cells and normal cells (untreated cells). Dual-luciferase reporter assays were conducted to verify the possible binding sites of microRNA (miR)-190a-3p on lncRNA PART1. In addition, NP cell viability and apoptosis were measured by performing MTT and flow cytometry, respectively. Expression and secretion of inflammatory factors (TNF-α, IL-1β and IL-6) and extracellular matrix (ECM) degradation-related proteins (aggrecan and collagen type II) were measured using ELISA, RT-qPCR and western blotting. Expression levels of lncRNA PART1 in LPS-treated NP cells were found to be higher compared with those in the control groups. miR-190a-3p directly targeted lncRNA PART1. PART1 knockdown enhanced cell viability, reduced cell apoptosis, inhibited inflammatory factor secretion and promoted ECM degradation in LPS-stimulated NP cells. However, transfection with the miR-190a-3p inhibitor reversed the aforementioned PART1 knockdown-induced alterations in cell viability, apoptosis, inflammatory cytokine and ECM degradation. Collectively, these results suggest that PART1 accelerates the progression of IDD by directly targeting miR-190a-3p, which provides a novel target for IDD diagnosis and treatment.
Keywords: intervertebral disc degeneration; long non-coding RNA prostate androgen-regulated transcript 1; microRNA-190a-3p.
Copyright: © Zhang et al.