RETRACTED: HOTAIR Accelerates Dyskinesia in a MPTP-Lesioned Mouse Model of PD via SSTR1 Methylation-Mediated ERK1/2 Axis

Abstract

Homeobox transcript antisense RNA (HOTAIR), has been associated with neuroprotective effects in Parkinson’s disease (PD). However, the underlying mechanisms still remain unclear. Hence, this present study attempted to clarify the functional relevance of HOTAIR in PD. We established an in vivo mouse model of PD using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and an in vitro cell model of PD by treating dopaminergic neuron MN9D cells with 1-methyl-4-phenylpyridinium species (MPP + ). The expressions of somatostatin receptor 1 (SSTR1) and HOTAIR were altered to examine their effects on MN9D cell viability and apoptosis, as well as on movement impairments in MPTP-induced PD mouse model. The results indicated that HOTAIR expression was upregulated and SSTR1 was downregulated in in vivo and in vitro PD models. HOTAIR could bind to the promoter region of SSTR1, resulting in an increase of SSTR1 methylation through the recruitment of DNA methyltransferases in PD cell models. Notably, overexpression of HOTAIR and silencing of SSTR1 enhanced dopaminergic neuron apoptosis in MN9D cells and exacerbated dyskinesia in MPTP-induced PD mouse model. Collectively, overexpressed HOTAIR stimulates DNA methylation of SSTR1 to reduce SSTR1 expression, thereby accelerating dyskinesia and facilitating dopaminergic neuron apoptosis in a MPTP-lesioned PD mouse model via activation of the ERK1/2 axis.

JMJD6–BRD4 complex stimulates lncRNA HOTAIR transcription by binding to the promoter region of HOTAIR and induces radioresistance in liver cancer stem cells

“…also uncovered that abnormal activation of ERK could increase the radioresistance of liver cancer cells [ 39 ]. In addition, overexpression of HOTAIR has been reported to accelerate dyskinesia and facilitate dopaminergic neuron apoptosis in a Parkinson’s disease mouse model via activation of the ERK1/2 axis [ 59 ]. Another study has shown that HOTAIR depletion can promote apoptosis of lymphoma cells via inactivation of the ERK signaling pathway [ 60 ].…”

Long Non-coding RNA HOTAIR in Central Nervous System Disorders: New Insights in Pathogenesis, Diagnosis, and Therapeutic Potential

“…In a PD cell model, HOTAIR bound to the promoter region of somatostatin receptor 1 (SSTR1), leading to increased methylation of SSTR1 by recruiting DNA methyltransferases. Notably, in a MPTP-induced PD mouse model, overexpressed HOTAIR stimulated DNA methylation of SSTR1 to reduce SSTR1 expression, thereby accelerating dyskinesia and facilitating dopaminergic neuron apoptosis ( Cai et al, 2020 ). LRRK2 gene mutations have been widely recognized as the most common cause of dominantly inherited PD and one of the risk factors for sporadic PD ( Tolosa et al, 2020 ).…”

LncRNA HOTAIR in exercise-induced neuro-protective function in Alzheimer’s disease

“…LncRNA HOTAIR has been broadly examined in numerous investigations. In in vivo and in vitro Parkinson's disease models, the expression of HOTAIR is enhanced and its' overexpression aggravates dyskinesia, which indicates that HOTAIR may participate in neuro-degenerative disorders [3].…”