A novel regulatory network among LncRpa, CircRar1, MiR-671 and apoptotic genes promotes lead-induced neuronal cell apoptosis

Aruo Nan, Lijian Chen, Nan Zhang, Zhenzhong Liu, Ti Yang, Zhishan Wang, Chengfeng Yang, Yiguo Jiang

Research output: Contribution to journalArticlepeer-review

96 Scopus citations

Abstract

Lead is a metal that has toxic effects on the developing nervous system. However, the mechanisms underlying lead-induced neurotoxicity are not well understood. Non-coding RNAs (ncRNAs) play an important role in epigenetic regulation, but few studies have examined the function of ncRNAs in lead-induced neurotoxicity. We addressed this in the present study by evaluating the functions of a long non-coding RNA (named lncRpa) and a circular RNA (named circRar1) in a mouse model of lead-induced neurotoxicity. High-throughput RNA sequencing showed that both lncRpa and circRar1 promoted neuronal apoptosis. We also found that lncRpa and circRar1 induced the upregulation of apoptosis-associated factors caspase8 and p38 at the mRNA and protein levels via modulation of their common target microRNA miR-671. This is the first report of a regulatory interaction among a lncRNA, circRNA, and miRNA mediating neuronal apoptosis in response to lead toxicity.

Original languageEnglish
Pages (from-to)1671-1684
Number of pages14
JournalArchives of Toxicology
Volume91
Issue number4
DOIs
StatePublished - Apr 1 2017

Bibliographical note

Funding Information:
We thank Dr. Sijin Liu (professor of Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences) for recommendations on the manuscript. This work was supported by the National Key Basic Research Program of China (No. 2012CB525004 to Y. G. J.), the National Natural Science Foundation of China (No. 21277036, 81573180, and 81172633 to Y. G. J.), the Key Program of Guangdong Natural Science Foundation (No. 2014A030311017 to Y. G. J.), the University Major Program of Guangdong (No. 2014SZD48 to Y. G. J.), the University Talent Program of Guangdong (No. 2013-164 to Y. G. J.), and the University Chief Scientist Program of Guangzhou (No. 1201541575 to Y. G. J.).

Publisher Copyright:
© 2016, The Author(s).

Keywords

  • Cell apoptosis
  • CircRNA
  • Lead
  • LncRNA
  • MiRNA
  • Neurotoxicity

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

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