MicroRNA-93 Regulates Hypoxia-Induced Autophagy by Targeting ULK1

Abstract EN

The expression of the core autophagy kinase, Unc51-like kinase 1 (ULK1), is regulated transcriptionally and translationally by starvation-induced autophagy.

However, how ULK1 is regulated during hypoxia is not well understood.

Previously, we showed that ULK1 expression is induced by hypoxia stress.

Here, we report a new ULK1-modulating microRNA, miR-93; its transcription is negatively correlated with the translation of ULK1 under hypoxic condition.

miR-93 targets ULK1 and reduces its protein levels under hypoxia condition.

miR-93 also inhibits hypoxia-induced autophagy by preventing LC3-I to LC3-II transition and P62 degradation; these processes are reversed by the overexpression of an endogenous miR-93 inhibitor.

Re-expression of ULK1 without miR-93 response elements restores the hypoxia-induced autophagy which is inhibited by miR-93.

Finally, we detected the effects of miR-93 on cell viability and apoptosis in noncancer cell lines and cancer cells.

We found that miR-93 sustains the viability of MEFs (mouse embryonic fibroblasts) and inhibits its apoptosis under hypoxia.

Thus, we conclude that miR-93 is involved in hypoxia-induced autophagy by regulating ULK1.

Our results provide a new angle to understand the complicated regulation of the key autophagy kinase ULK1 during different stress conditions.