MicroRNA-495 regulates starvation-induced autophagy by targeting ATG3
MicroRNA-495 regulates starvation-induced autophagy by targeting ATG3
复制标题
MicroRNA-495 通过靶向 ATG3 调节饥饿诱导的自噬。
DOI：
10.1002/1873-3468.12108
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发表时间：
2016-03-01
期刊：
影响因子：
3.5
通讯作者：
Feng, Du
中科院分区：
文献类型：
--
作者：
Li, Wen;Yang, Yue;Feng, Du
一些重要的自噬基因的功能受到microRNA的调控。然而，ATG 3调节microRNA从未被报道过。在这里，我们表明，在营养缺乏或雷帕霉素处理的条件下，miR-495的转录与ATG 3的翻译呈负相关。miR-495靶向ATG 3并在饥饿条件下调节其蛋白水平。miR-495还通过减少自噬体的数量和阻止LC 3-I-to-LC 3-II转换和P62降解来抑制饥饿诱导的自噬。这些过程被内源性miR-495抑制剂的过表达逆转。无miR-495应答元件的Atg 3的再表达恢复了miR-495抑制的自噬。miR-495在饥饿条件下维持细胞活力，但在缺氧条件下没有影响。此外，miR-495抑制依托泊苷诱导的细胞死亡。总之，miR-495通过调节Atg 3参与饥饿诱导的自噬。
The functions of some essential autophagy genes are regulated by microRNAs. However, an ATG3-modulating microRNA has never been reported. Here we show that the transcription of miR-495 negatively correlates with the translation of ATG3 under nutrient-deprived or rapamycin-treated conditions. miR-495 targets ATG3 and regulates its protein levels under starvation conditions. miR-495 also inhibits starvation-induced autophagy by decreasing the number of autophagosomes and by preventing LC3-I-to-LC3-II transition and P62 degradation. These processes are reversed by the overexpression of an endogenous miR-495 inhibitor. Re-expression of Atg3 without miR-495 response elements restores miR-495-inhibited autophagy. miR-495 sustains cell viability under starvation conditions but has no effect under hypoxia. Moreover, miR-495 inhibits etoposide-induced cell death. In conclusion, miR-495 is involved in starvation-induced autophagy by regulating Atg3.