Long non‐coding RNA Opa interacting protein 5‐antisense RNA 1 promotes mitochondrial autophagy and protects SH‐SY5Y cells from 1‐methyl‐4‐phenylpyridine‐induced damage by binding to microRNA‐137 and upregulating NIX

Abstract

Abstract Parkinson's disease (PD) is a leading cause of disability. Long noncoding RNA (LncRNA) OIP5‐AS1 alleviates the accumulation and toxicity of 1‐methyl‐4‐phenylpyridine (MPP+)/‐induced α‐synuclein in human neuroblastoma SH‐SY5Y cells, which may be involved in the pathological process of PD. This study explored the neuroprotective effect of lncRNA OIP5‐AS1 on MPP+/‐induced SH‐SY5Y cell model of PD, so as to provide a theoretical basis for PD treatment. The PD cell model was established (MPP+ group). The overexpression vector oe‐OIP5‐AS1 was constructed and transfected into MPP+/‐induced SH‐SY5Y cells, which were further transfected with miR‐137 mimic or si‐NIX plasmids. The localization of OIP5‐AS1 and its binding sites with miR‐137 were predicted by subcellular isolation and fluorescence in situ hybridization analysis. The targeting relationships between OIP5‐AS1 and miR‐137, and miR‐137 and NIX were detected by dual‐luciferase reporter assays. The mitochondrial membrane potential (Δψm) and total reactive oxygen species (ROS) levels, and expressions of α‐synuclein, inflammatory cytokines, and microglia‐activated chemokines, cell activity, and apoptosis were assessed. OIP5‐AS1 was downregulated in MPP+ cells. After OIP5‐AS1 overexpression, miR‐137 was downregulated and NIX was upregulated in MPP+ cells, inflammatory factors and chemokines were downregulated. There were target relationships between OIP5‐AS1 and miR‐137, and miR‐137 and NIX. After OIP5‐AS1 overexpression, miR‐137 overexpression or NIX downregulation inhibited mitochondrial autophagy and ROS levels and aggravated mitochondrial vacuolation; and partially reversed the effect of OIP5‐AS1 overexpression on promoting mitochondrial autophagy and protection on MPP+ cells. Collectively, lncRNA OIP5‐AS1 promoted NIX expression through competitively binding to miR‐137, and promoted mitochondrial autophagy, thus protecting neurons from degeneration which might be seen in patients with PD.

Keywords

• BNIP3L
• miR‐137
• NIX
• OIP5‐AS1
• Parkinson's disease