MiR-122-5p and miR-326-3p promote cadmium-induced NRK-52E cell apoptosis by downregulating PLD1

摘要

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 down-regulating PLD1 expression.