State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing, China.
PLoS One. 2013 Jul 23;8(7):e69351. doi: 10.1371/journal.pone.0069351. Print 2013.
SOD2 (superoxide dismutase 2) is one of the endogenous antioxidant enzymes that protect against reactive oxygen species. While explorations of SOD2 expression regulation are mainly focused on transcriptional and post-translational activation, there are few reports about the post-transcriptional regulation of SOD2. MicroRNAs (miRNAs) are 21nt-25nt (nucleotide) small noncoding RNAs that have emerged as indispensable regulators of gene expression. Here we show that miR-146a, a widely expressed miRNA, is up-regulated by H2O2-induced stress. By sequence analysis we found a binding site for miR-146a in the sod2 mRNA 3'UTR, and a luciferase reporter assay confirmed that miR-146a can interact with this sod2 regulatory region. Our results further show that miR-146a could down-regulate the SOD2 protein expression, and antisense-miR-146a could reverse the decrease of both the SOD2 level and cell viability in H2O2 treated PC12 cells. In conclusion, here we have identified a novel function of miR-146a in the post-transcriptional regulation of SOD2 expression.
SOD2（超氧化物歧化酶 2）是一种内源性抗氧化酶，可抵抗活性氧。虽然 SOD2 表达调控的研究主要集中在转录和翻译后激活上，但关于 SOD2 的转录后调控的报道很少。微小 RNA（miRNA）是 21nt-25nt（核苷酸）的小非编码 RNA，已成为基因表达不可或缺的调控因子。在这里，我们发现广泛表达的 miRNA 之一 miR-146a 可被 H2O2 诱导的应激上调。通过序列分析，我们在 sod2 mRNA 3'UTR 中发现了一个 miR-146a 的结合位点，荧光素酶报告基因检测证实 miR-146a 可以与这个 sod2 调节区域相互作用。我们的结果进一步表明，miR-146a 可以下调 SOD2 蛋白的表达，而反义 miR-146a 可以逆转 H2O2 处理的 PC12 细胞中 SOD2 水平和细胞活力的降低。总之，我们在这里确定了 miR-146a 在 SOD2 表达的转录后调控中的新功能。
