Overexpression of REST has been implicated in brain tumors, ischemic insults, epilepsy, and movement disorders such as Huntington's disease. However, owing to the lack of a conditional REST overexpression animal model, the mechanism of action of REST overexpression in these disorders has not been established in vivo. We created a REST overexpression mouse model using the human REST (hREST) gene. Our results using these mice confirm that hREST expression parallels endogenous REST expression in embryonic mouse brains. Further analyses indicate that REST represses the dopamine receptor 2 (Drd2) gene, which encodes a critical nigrostriatal receptor involved in regulating movement, in vivo. Overexpression of REST using Drd2-Cre in adult mice results in increased REST and decreased DRD2 expression in the striatum, a major site of DRD2 expression, and phenocopies the spontaneous locomotion deficits seen upon global DRD2 deletion or specific DRD2 deletion from indirect-pathway medium spiny neurons. Thus, our studies using this mouse model not only reveal a new function of REST in regulating spontaneous locomotion but also suggest that REST overexpression in DRD2-expressing cells results in spontaneous locomotion deficits.
The long non-coding RNA (lncRNA), HAR1A is emerging as a putative tumour suppressor. In non-neoplastic brain cells, REST suppresses HAR1A expression. In gliomas REST acts as an oncogene and is a potential therapeutic target.
Given the high recurrence rate of kidney stones, surgical lithotripsy and stone removal are not the ultimate treatments for kidney stones. There's an urgent need to explore the genetic mechanisms behind the susceptibility to kidney stones and to identify potential targets for prevention, to reduce the renal damage caused by recurrent stone formation. In this study, we screened 4548 circulating proteins using proteome-wide Mendelian Randomization (MR) to find proteins with a causal relationship to kidney stone risk.
RE-1 silencing transcription factor (REST) is a key repressor of neural genes. REST is upregulated under stress signals, aging and neurodegenerative diseases, but although it is upregulated, its function is lost in Alzheimer's Disease. However, why it becomes inactive remains unclear.
Breast cancer has become the leading cause of death in women. Membrane associated ring-CH-type finger 1 (MARCHF1) is associated with the development of various types of cancer, but the exact role of MARCHF1 in breast cancer remains unclear. In our study, the higher MARCHF1 expression was observed in tumor samples of patients with breast cancer and then the role of MARCHF1 in breast cancer was further evaluated.
Objective: This study aims to investigate the expression profile of miRNAs significantly dysregulated after acute myocardial infarction (AMI) and their potential targets.
Methods: After the establishment of a mouse model of AMI, RNA was extracted from mouse infarcted myocardium. Paired-end sequencing was then performed using the Illumina NovaSeq 6000 system to explore the expression profile of miRNAs.
