Dysregulation of Long Non-coding RNAs-the Novel lnc in Metal Toxicity and Carcinogenesis

Metals are common environmental pollutants. Acute and chronic exposures to non-essential toxic metals or excessive essential metals cause various diseases including cancer in humans. However, the underlying mechanisms have not been well understood. Long non-coding RNAs (lncRNAs) refer to RNA transcripts that have more than 200 nucleotides but do not have significant protein coding capacities. While lncRNAs were once considered transcription noise, they have become increasingly recognized as crucial players in various physiological and pathogenesis processes. The goal of this article is to review and discuss recent studies that show important roles of lncRNA dysregulations in metal toxicity and carcinogenesis.

Recent studies showed that metal exposures dysregulate expression of lncRNAs in cultured cells, animals and humas. However, only a few studies determined the mechanisms of how metal exposure dysregulated expression of lncRNAs. The majority of the studies reported the association of abnormally expressed lncRNAs with various toxic effects of metal exposures, only limited studies established causal relationships demonstrating causal roles of dysregulated lncRNAs in metal toxicity and carcinogenesis. Mechanistically, most studies reported that dysregulated lncRNAs functioned as microRNA sponges to regulate gene expression, much less studies explored other mechanisms of lncRNA actions. It is evident that metal exposures dysregulate expression of lncRNAs, which may serve as novel mediators in metal toxicity and carcinogenesis. Further studies are needed to establish dysregulated lncRNAs as potential diagnostic biomarkers and therapeutic targets for metal exposure-associated diseases.