Abstract Cadmium (Cd) as a heavy metal causes serious environmental pollution and multiple organ and system damage in human. However, little is known about the specific molecular mechanisms of the associated regulatory networks. In this study, we selected Caenorhabditis elegans ( C. elegans ) to investigate the effects of Cd exposure as it acts as an acknowledged and established genetic model organism. A total of 26 differentially-expressed circular RNA (DEcircRNAs), 143 lncRNAs (DElncRNAs), 69 microRNAs (DEmiRNAs) and 6209 mRNAs (DEmRNAs) were found and identified, which might influence reproductive function, aging processes and nervous system functions through regulating the levels of circRNAs and lncRNAs and the controlling of regulatory networks of circRNA/lncRNA-miRNA-mRNA. Based on quantitative PCR, four DEcircRNAs and three DElncRNAs were confirmed to have different expression levels between the Cd-treated and control group. Further, 5 protein-coding genes might be regulated by DElnRNAs through cis-acting and 114 by trans-acting elements. Additionally, 42 differentially regulative phosphopeptides were detected and 4 novel pairs of transcription factors (TFs)-kinase-substrate that might be influenced by Cd exposure were constructed by phosphoproteomics. Our findings suggest that Cd might influence multi-functions and the aging process of C. elegans and may inhibit the expression of TFs to reduce phosphorylated levels of the corresponding protein. Synopsis Cadmium exists widely in soil, water and air. This study manifested the regulatory network involving circRNA, lncRNA and phosphorylated protein in C.elegans after Cd exposure, which revealing the potential molecular mechanism underlying the toxic effect caused by Cd. Graphic Abstract

Cadmium is detrimental to Caenorhabditis elegans via a network involving circRNA, lncRNA and phosphorylated protein