A transcribed ultraconserved noncoding RNA, Uc.173, is a key molecule for the inhibition of lead-induced neuronal apoptosis

Aruo Nan; Xinke Zhou; Lijian Chen; Meiling Liu; Nan Zhang; Li Zhang; Yuanwei Luo; Zhenzhong Liu; Lijun Dai; Yiguo Jiang

doi:10.18632/oncotarget.6590

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Research Papers: Pathology:

A transcribed ultraconserved noncoding RNA, Uc.173, is a key molecule for the inhibition of lead-induced neuronal apoptosis

Aruo Nan, Xinke Zhou, Lijian Chen, Meiling Liu, Nan Zhang, Li Zhang, Yuanwei Luo, Zhenzhong Liu, Lijun Dai and Yiguo Jiang _

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Oncotarget. 2016; 7:112-124. https://doi.org/10.18632/oncotarget.6590

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Abstract

Aruo Nan1,*, Xinke Zhou2,*, Lijian Chen1, Meiling Liu1, Nan Zhang1, Li Zhang3, Yuanwei Luo2, Zhenzhong Liu1, Lijun Dai4 and Yiguo Jiang1

1 State Key Laboratory of Respiratory Disease, Institute for Chemical Carcinogenesis, Guangzhou Medical University, Guangzhou, PR China

2 Institute for Chemical Carcinogenesis, The Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, PR China

3 School of Public Health, Guangdong Pharmaceutical University, Guangzhou, PR China

4 Laboratory Animal Center, Guangzhou Medical University, Guangzhou, PR China

* These authors have contributed equally to this work

Correspondence to:

Yiguo Jiang, email:

Keywords: Uc.173, T-UCR, lead, neuronal apoptosis, Pathology Section

Received: September 14, 2015 Accepted: November 26, 2015 Published: December 13, 2015

Abstract

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.

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Research Papers: Pathology:

A transcribed ultraconserved noncoding RNA, Uc.173, is a key molecule for the inhibition of lead-induced neuronal apoptosis

Abstract