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

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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00204-016-1837-1) contains supplementary material, which is available to authorized users.