MiRNAs have recently been implicated in the regulation of autophagy. The present study focuses on how
miRNA expression profiling is linked to the regulation of
starvation-induced autophagy. Atg5 wild-type (WT) and knockout (KO) mouse embryonic fibroblasts (MEFs) were starved in Earle's balanced
salt solution (EBSS) for 3h, and
miRNA microarray was then performed to compare the
miRNA expression profiles. Our results showed that: (1) one hundred
miRNAs were significantly altered in both Atg5 WT and KO MEFs during
starvation-induced autophagy; (2) among those
miRNAs with significant changes upon
starvation, 60 of them were upregulated in both Atg5 WT and KO MEFs and only 24
miRNAs were upregulated exclusively in Atg5 KO MEFs; (3) qRT-PCR validation analysis of 8 selected
miRNAs showed a high correlation coefficient (r=0.95456) with microarray results; (4) many significantly altered
miRNAs were mapped to several key signaling pathways and autophagy-related genes (Atgs) involved in the autophagy process, including (i) the Beclin1-Class III
phosphatidylinositol 3-kinase (PI3KC3) complex, (ii) the ULK1
complex, (iii) the RAG/mechanistic target of
rapamycin (mTOR) pathway, (iv) the liver
kinase B1 (LKB1)-AMP-activated
protein kinase (AMPK)-mTOR, and the
class I phosphatidylinositol 3-kinase (PI3KC1)-Akt-mTOR pathways. The systematical analysis of the
miRNA expression profiling and preliminary network analysis reveal that most of these
miRNAs play important roles in autophagy regulation. Our results clearly demonstrate that
miRNAs are involved in the autophagy process and understanding the functions of
miRNAs provides novel insights into the molecular mechanisms underlying
starvation-induced autophagy.