Neuroprotective Role of MicroRNA-22 in a 6-Hydroxydopamine-Induced Cell Model of Parkinson’s Disease via Regulation of Its Target Gene TRPM7

Abstract

Parkinson's disease (PD), the second most prevalent neurodegenerative disorder with only symptomatic treatment available, is characterized by a progressive loss of dopaminergic neurons in the midbrain. Ample evidence indicated that microRNAs (miRs) could regulate post-transcriptional gene expression and neuronal disease. In the present study, we have evaluated the effects and mechanism of miR-22 in PC12 pheochromocytoma cells treated with 6-hydroxydopamine (6-OHDA) to mimic PD. RT-PCR results showed that the expression of miR-22 is downregulated in 6-OHDA-treated PC12 cells, and the overexpression of miR-22 significantly promoted the survival and proliferation of 6-OHDA-induced PC12 cells, whereas miR-22 inhibitor reversed these effects. In addition, PC12 cells were treated with miR-22 mimics or inhibitor following 6-OHDA administration, which medicated ROS production and upregulation or downregulation of caspase-3 activity, respectively. A luciferase reporter assay revealed that transient receptor potential melastatin 7 (TRPM7) is a direct target gene of miR-22, and miR-22 overexpression markedly downregulated the level of TRPM7. Strikingly, further analysis showed that miR-22 mediated 6-OHDA-induced PC12 cell survival and proliferation by targeting TRPM7. Taken together, the present study showed that miR-22 overexpression exhibited neuroprotective and reversal effects on the 6-OHDA-induced PC12 cell growth and apoptosis by targeting TRPM7.

Circular RNA cZNF292 silence alleviates OGD/R-induced injury through up-regulation of miR-22 in rat neural stem cells (NSCs)

“…Multiple miRNAs are abundant in the nervous system and serve key functions in brain developmental plasticity [30]. Currently, accumulating evidence has uncovered the different functions of miRNAs in various neurological diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and I/R [16,[31][32][33][34]. A similar research explored the neuro-protective effect of miR-22 overexpression in vitro and in vivo experiments [33].…”

miR-135b Plays a Neuroprotective Role by Targeting GSK3β in MPP+-Intoxicated SH-SY5Y Cells

“…miR-22 overexpression exhibited neuroprotective and reversal effects on a 6-hydroxydopamine- (6-OHDA-) induced cell model of PD by targeting transient receptor potential melastatin 7 (TRPM7) [29]. miR-7 modulated Nod-like receptor protein 3- (NLRP3-) mediated neuroinflammation in the pathogenesis of PD [30].…”

Validation of Differentially Expressed Brain-Enriched microRNAs in the Plasma of Parkinson’s Disease Patients

“…miR-22-3p targets GBA, which encodes for β-glucocerebrosidase, a lysosomal enzyme involved in sphingolipid degradation; mutations in GBA are the single largest risk factor for PD [25]. In addition, miR-22 is neuroprotective in multiple neurodegeneration and traumatic brain injury models, has regenerative capabilities, and is involved in several aspects of neuronal development including cell cycle length, polarization of migrating neurons, and long-term synaptic plasticity [26][27][28]. miR-124-3p is the most abundant neuronal miRNA in the nervous system, and is considered indispensable for neuronal fate determination, differentiation, and plasticity [29,30].…”