Parkinsons Disease

HAGLR[LncRNA]

miR-130a-3p[miRNA]

MeCP2[mRNA]

Sh-Sy5Y Cells

Homo sapiens (human)

Open Med (Wars). 2021 Aug 5;16(1):1121-1131. doi: 10.1515/med-2021-0301. eCollection 2021.

HAGLR promotes neuron differentiation through the miR-130a-3p-MeCP2 axis.

microarray;Western blot;luciferase assay;

Parkinson's disease (PD) is a prevalent neurodegenerative disease. Currently, the molecular mechanisms underlying the progressions of PD are not fully understood. The human neuroblastoma cell line SH-SY5Y has been widely used as an in vitro model for PD. This study aims to investigate the molecular mechanisms of the non-coding RNA-mediated SH-SY5Y differentiation induced by retinoic acid (RA). By microArray analysis, lncRNA HAGLR was observed to be significantly upregulated during the RA-induced SH-SY5Y differentiation. Silencing HAGLR blocked the RA-induced SH-SY5Y differentiation. Moreover, bioinformatical analysis illustrated that miR-130a-3p contains binding sites for HAGLR. The RNA-pull down assay and luciferase assay demonstrated that HAGLR functioned as a ceRNA of miR-130a-3p in SH-SY5Y cells. Overexpression of miR-130a-3p effectively inhibited SH-SY5Y differentiation. We identified MeCP2, a vital molecule in neuronal diseases, to be a direct target of miR-130a-3p in SH-SY5Y cells by western blot and luciferase assays. The rescue experiments verified that recovery of miR-130a-3p in HAGLR-overexpressing SH-SY5Y cells could successfully overcome the RA-induced SH-SY5Y differentiation by targeting MeCP2. In summary, this study reveals a potential molecular mechanism for the lncRNA-HAGLR-promoted in vitro neuron differentiation by targeting the miR-130a-3p-MeCP2 axis, contributing to the understanding of the pathogenesis and progression of PD.