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.

中文翻译：

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MiR-122-5p和miR-326-3p通过下调PLD1促进镉诱导的NRK-52E细胞凋亡

镉是一种有毒重金属，广泛分布于环境和制造业中。长期接触镉被认为是肾损伤的风险，最终会导致慢性肾病。磷脂酶 D1 (PLD1) 促进细胞增殖并抑制细胞凋亡，并可能参与镉诱导的肾损伤。在本研究中，我们使用 miRNA 微阵列分析和生物信息学分析来鉴定 miRNA，这些 miRNA 可能调节 PLD1 表达并对镉诱导的肾损伤产生影响。MiR-122-5p 和 miR-326-3p 被选为候选者，使用 NRK-52E 细胞探索它们在肾损伤中的调节功能。在暴露于镉 6 周后，这两种 miRNA 在 SD 大鼠的肾脏中均表现出更高的表达。镉处理还增加了 miR-122-5p 和 miR-326-3p，并降低了 NRK-52E 细胞中的 PLD1。miR-122-5p 和 miR-326-3p 都可以通过靶向其 3'UTR 下调 PLD1 表达并增强镉诱导的细胞凋亡，而抑制这两种 miRNA 中的任何一种都可以逆转这种作用。总之，我们的结果表明 miR-122-5p 和 miR-326-3p 可能通过下调 PLD1 表达来增强镉诱导的 NRK-52E 细胞凋亡。