The oncogene c-MYC directly activates miR-17/92 gene expression. In addition, E2F1 and E2F3 also activate the transcription of miR-17/92 cluster, suggesting that miR-17/92 plays key roles in regulating cell proliferation.38, 39 By contrast, the tumor suppressor TP53 transcriptionally represses miR-17/92 expression, through binding to the TATA box of the miR-17/92 promoter.40 A recent study report that both two members of the miR-17/92 cluster, miR-20a and miR-17, target the TP53-activating kinase DAPK3, which leads to inactivation of TP53 and upregulation of the miR-17/92 cluster.41 Several studies demonstrate that miR-20a promotes proliferation, sustains cell survival and increases angiogenesis by targeting a number of genes, including the E2F family members.28, 42, 43 However, in some circumstances, which depends on the physiological context and the cell type, miR-20a plays tumor suppressive function.44, 45, 46 Our results show that miR-20a inhibits nutrient starvation-induced autophagic flux. miR-20a suppresses autophagy and lysosomal activity through downregulating the expression of ATG16L1, BECN1 and SQSTM1. Autophagy-deficient cells have deregulated ROS and accumulate DNA damage, which possibly contribute to genome instability and tumor-initiating capacity (Figure 8d).