A transcribed ultraconserved noncoding RNA, Uc.173, is a key molecule for the inhibition of lead-induced neuronal apoptosis
research target：Ultra-conserved lncRNA
Periodicals：Oncotarget
IF：6.359
Cooperative Unit：Guangzhou Medical University
Time of publication：December，2015
Summary
As a common toxic metal, lead has significant neurotoxicity to brain development. Long non-coding RNAs (lncRNAs) function in multiple biological processes. However, whether lncRNAs are involved in lead-induced neurotoxicity remains unclear. Uc.173 is a lncRNA from a transcribed ultra-conservative region (T-UCR) of human, mouse and rat genomes. We established a lead-induced nerve injury mouse model. It showed the levels of Uc.173 decreased significantly in hippocampus tissue and serum of the model. We further tested the expression of Uc.173 in serum of lead-exposed children, which also showed a tendency to decrease. To explore the effects of Uc.173 on leadinduced nerve injury, we overexpressed Uc.173 in an N2a mouse nerve cell line and found Uc.173 had an inhibitory effect on lead-induced apoptosis of N2a. To investigate the molecular mechanisms of Uc.173 in apoptosis associated with lead-induced nerve injury, we predicted the target microRNAs of Uc.173 by using miRanda, TargetScan and RegRNA. After performing quantitative real-time PCR and bioinformatics analysis, we showed Uc.173 might inter-regulate with miR-291a-3p in lead-induced apoptosis and regulate apoptosis-associated genes. Our study suggests Uc.173 significantly inhibits the apoptosis of nerve cells, which may be mediated by inter-regulation with miRNAs in lead-induced nerve injury.
Research Background
Metal lead poisoning has caused significant harm in the population, especially in children, and studies have shown that lead acts as a strong neurodevelopmental poison. Lead poisoning will cause neuronal necrosis. In recent years, many studies have shown that lncRNAs play an important role in exogenous carcinogenesis, but no report has been reported on lead-induced nerve damage. Studies have shown that some transcribed ultra-conserved genes, such as Uc.73 and Uc.338, can act as tumor proteins to promote cancer cell growth. Through lncRNA chip analysis, it was found that the expression level of ultra-conserved lncRNA Uc.173 changed with the change of target genes. In order to study the role of Uc.173 in lead-induced nerve injury, this paper overexpressed Uc.173 in mouse brain tissue and serum, and detected the expression of lncRNA in the tissue. At the same time, the human serum exposed to lead was detected. Using mouse nerve cell N2a to further explore the role of Uc.173 in lead-induced neuronal apoptosis.
Partial results of cooperation
1、Detection of the expression of Uc.173 in hippocampus tissue and serum of lead-exposed mouse as well as the serum of lead-exposed population by qRT-PCR.After being exposed to lead for five weeks, the expression of Uc.173 in hippocampus tissue (A. and B.), in mouse serum (C. and D.), as well as in lead-exposed human serum (E. and F.).
2、Expression of Uc.173 in N2a nerve cells of lead-exposed mouse and detection of apoptotic markers.
3、Expression of nine target miRNAs with highest potential in different groups.
References
Nan A, Zhou X, Chen L, et al. A transcribed ultraconserved noncoding RNA, Uc.173, is a key molecule for the inhibition of lead-induced neuronal apoptosis[J].
Oncotarget, 2015, 7(1):112-124.
