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.

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.

Zhao Y ，Xie Y ，Yao WY ，Wang YY ，Song N ... -  《-》

Down-Regulation of ID2-AS1 Alleviates the Neuronal Injury Induced by 1-Methy1-4-Phenylpyridinium in Human Neuroblastoma Cell Line SH-SY5Y Cells Through Regulating miR-199a-5p/IFNAR1/JAK2/STAT1 Axis.

Xu F ，Wang H ，Tian J ，Xu H ... -  《-》

LncRNA OIP5-AS1 reduces α-synuclein aggregation and toxicity by targeting miR-126 to activate PLK2 in human neuroblastoma SH-SY5Y cells.

It has been reported that many long noncoding RNAs (lncRNA) are abnormally expressed in Parkinson's disease (PD). However, the knowledge about the role of dysregulated lncRNA in the pathological process of PD and the potential molecular regulation mechanism is still limited. Our immunofluorescence data show that miR-126 enhances the aggregation and toxicity of synuclein, while lncRNA OIP5-AS1 reduces the aggregation and toxicity of MPP + induced α-synuclein by targeting miR-126. Luciferase experiments have found that miR-126 regulates α-synuclein by targeting PLK2. Western blot and IP experimental analysis showed that this process is achieved by regulating PLK2/α-synuclein autophagy. In conclusion, our data indicate that OIP5-AS1 promotes the autophagy of PLK2-α-synuclein by targeting the miR-126 axis with pathogenic factors, thus reducing the aggregation toxicity of α-synuclein, which It will help better to understand the mechanism of dopaminergic neuron loss in PD and provide novel treatment options.

Song Z ，Xie B 《-》

LncRNA SNHG1 promotes α-synuclein aggregation and toxicity by targeting miR-15b-5p to activate SIAH1 in human neuroblastoma SH-SY5Y cells.

Numerous long non-coding RNAs (lncRNAs) have been identified as aberrantly expressed in Parkinson's disease (PD). However, limited knowledge is available concerning the roles of dysregulated lncRNAs and the underlying molecular regulatory mechanism in the pathological process of PD. In this study, we found that lncRNA small nucleolar RNA host gene 1 (SNHG1) and seven in absentia homolog 1 (SIAH1) were upregulated, but microRNA-15b-5p (miR-15b-5p) was downregulated in SH-SY5Y cells pretreated with MPP+, as well as in MPTP-induced mouse model of PD. Overexpression of SIAH1 enhanced cellular toxicity of α-synuclein in SH-SY5Y cells, as indicated by the reduction of cell viability and elevation of LDH release. The percentage of α-synuclein aggregate-positive cells and the number of α-synuclein aggregates per cell were increased in SH-SY5Y cells transfected with pcDNA-SIAH1, while decreased after transfection with short interfering RNA specific for SIAH1 (si-SIAH1). Bioinformatics and luciferase reporter assay revealed that SIAH1 was a direct target of miR-15b-5p. We also found that SNHG1 could directly bind to miR-15-5p and repress miR-15-5p expression. Upregulation of miR-15b-5p alleviated α-synuclein aggregation and apoptosis by targeting SIAH1 in SH-SY5Y cells overexpressing α-synuclein. Overexpression of SNHG1 enhanced, whereas SNHG1 knockdown inhibited α-synuclein aggregation and α-synuclein-induced apoptosis. Moreover, the neuroprotective effect of si-SNHG1 was abrogated by downregulation of miR-15b-5p. In summary, our data suggest that SNHG1, as a pathogenic factor, promotes α-synuclein aggregation and toxicity by targeting the miR-15b-5p/SIAH1 axis, contributing to a better understanding of the mechanisms of Lewy body formation and loss of dopaminergic neurons in PD.

Chen Y ，Lian YJ ，Ma YQ ，Wu CJ ，Zheng YK ，Xie NC ... -  《-》

SNHG1 promotes MPP(+)-induced cytotoxicity by regulating PTEN/AKT/mTOR signaling pathway in SH-SY5Y cells via sponging miR-153-3p.

Zhao J ，Geng L ，Chen Y ，Wu C ... -  《-》