Unveiling the regulatory of miR-101-3p on ZNF746 in a Parkinson's disease cell model: Implications for therapeutic targeting

In this study, we explored the regulatory role of microRNA miR-101-3p on the zinc finger protein 746 (ZNF746), also known as PARIS, which is implicated in both sporadic and familial forms of Parkinson's disease. In a Parkinson's disease cell model, utilizing SH-SY5Y cells treated with 1-methyl-4-phenylpyridine (MPP+), we observed that miR-101–3p was downregulated, while ZNF746 was upregulated. To investigate the direct impact of miR-101-3p on ZNF746, our team conducted overexpression experiments, successfully reversing ZNF746's expression at both the mRNA and protein levels, as confirmed through quantitative PCR and western blotting. We also performed luciferase assays, providing compelling evidence that ZNF746 is a direct target of miR-101-3p. Additionally, we noted that miR-101-3p overexpression resulted in increased expression of PGC1α, a gene targeted by ZNF746. Functionally, we assessed the implications of miR-101-3p overexpression through MTS assays and flow cytometry, revealing significant promotion of cell viability, inhibition of ROS production, and reduced apoptosis in the Parkinson's disease cell model. In conclusion, this study highlights the role of miR-101-3p in regulating ZNF746 expression and suggests its potential as a therapeutic target for Parkinson's disease. These findings provide valuable molecular insights that could pave the way for innovative treatment strategies in combating this debilitating neurodegenerative disorder. •MiR-101-3p downregulation and ZNF746 upregulation imply Parkinson's involvement.•Luciferase assays confirm direct miR-101-3p targeting and ZNF746 modulation.•MiR-101-3p overexpression counters ZNF746, implying Parkinson's therapy.•MiR-101-3p boosts cell viability and reduces apoptosis for protection.•MiR-101-3p's role in ZNF746 and downstream targets uncovers Parkinson's treatments.