Cadmium is a toxic heavy metal distributed broadly in the environment and manufactory industry. Long‐term exposure to cadmium, considered as a risk for kidney injury, leads to chronic kidney disease eventually. Phospholipase D1 (PLD1) promotes cell proliferation and inhibits apoptosis, and might be involved in cadmium‐induced kidney injury. In this study, we used miRNA microarray assays and bioinformatics analysis to identify miRNAs, which may regulate PLD1 expression and exert an impact on cadmium‐induced kidney injury. MiR‐122‐5p and miR‐326‐3p，selected as candidates, were explored for their regulatory functions in kidney injury, using NRK‐52E cells. Both of these two miRNAs exhibited higher expression in kidneys of SD rats after exposure to cadmium for 6 weeks. Cadmium treatment also increased miR‐122‐5p and miR‐326‐3p and decreased PLD1 in NRK‐52E cells. Both of miR‐122‐5p and miR‐326‐3p could downregulate PLD1 expression through targeting its 3′UTR and enhance cadmium‐induced apoptosis, while inhibiting either of these two miRNAs could reverse such effects. In conclusion, our results suggest that miR‐122‐5p and miR‐326‐3p might enhance cadmium‐induced NRK‐52E cell apoptosis through downregulating PLD1 expression.

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