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

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