Search

Lead is a heavy metal pollutant that is widely present in the environment and can seriously harm human health, especially the nervous system. Long noncoding RNAs (lncRNAs) play important roles in many physiological and pathological processes; however, there remains a lack of in-depth studies on the molecular mechanisms associated with lead neurotoxicity. Here, our results showed that lead exposure inhibited cell proliferation and promoted cell apoptosis. We observed that lncRNAL20992 was significantly upregulated in a lead-induced neuronal-injury cell model according to quantitative reverse transcription polymerase chain reaction. Silencing lncRNAL20992 revealed its significant functions involved in promoting cell apoptosis and inhibiting cell proliferation according to cell-counting kit-8, EdU assay, terminal deoxynucleotidyl transferase dUTP nick-end labeling, and western blot. To elucidate the molecular mechanisms of lncRNAL20992, we used RNA pulldown mass spectrometry combined with bioinformatics analysis to discover 4 proteins (AIFM1, HSP7C, GRP78, and LMNA) that interacted with lncRNAL20992. Western blot analysis indicated that lncRNAL20992 involved in lead-induced neuronal injury was mediated by the 4 proteins. Our study constitutes the first investigation of the functions and related mechanisms of lncRNAL20992 and offered valuable insight into understanding the roles of lncRNA in lead-induced neurotoxicity., (© The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

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 lead-induced 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.

Lead is a heavy metal pollutant that is widely present in the environment and can seriously harm human health, especially the nervous system. Long noncoding RNAs (lncRNAs) play important roles in many physiological and pathological processes; however, there remains a lack of in-depth studies on the molecular mechanisms associated with lead neurotoxicity. Here, our results showed that lead exposure inhibited cell proliferation and promoted cell apoptosis. We observed that lncRNAL20992 was significantly upregulated in a lead-induced neuronal-injury cell model according to quantitative reverse transcription polymerase chain reaction. Silencing lncRNAL20992 revealed its significant functions involved in promoting cell apoptosis and inhibiting cell proliferation according to cell-counting kit-8, EdU assay, terminal deoxynucleotidyl transferase dUTP nick-end labeling, and western blot. To elucidate the molecular mechanisms of lncRNAL20992, we used RNA pulldown mass spectrometry combined with bioinformatics analysis to discover 4 proteins (AIFM1, HSP7C, GRP78, and LMNA) that interacted with lncRNAL20992. Western blot analysis indicated that lncRNAL20992 involved in lead-induced neuronal injury was mediated by the 4 proteins. Our study constitutes the first investigation of the functions and related mechanisms of lncRNAL20992 and offered valuable insight into understanding the roles of lncRNA in lead-induced neurotoxicity. [ABSTRACT FROM AUTHOR]