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

103 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

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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