miRNAs play a key role in the regulation of gene networks in mammalian cells. However, little is known about their roles and functions in the apoptosis pathway. Here, we conducted… Click to show full abstract
miRNAs play a key role in the regulation of gene networks in mammalian cells. However, little is known about their roles and functions in the apoptosis pathway. Here, we conducted a whole-genome miRNA screening for apoptosis and identified more than 100 miRNAs as apoptosis inducers. To further explain the roles of these mRNAs in apoptosis, a second round of screening was conducted between p53 +/+ and –/– cells. Among the hits, miR-596 was identified as a regulator of p53. The overexpression of miR-596 significantly increased p53 at the protein level, thereby inducing apoptosis. We also demonstrated that Smurf1 was the direct target of miR-596. Previously, Smurf1 was reported to attenuate the level of p53 through binding and stabilizing MDM2, a p53 inhibitor. Consequently, by targeting Smurf1, miR-596 indirectly increased the p53 level in mammalian cells. Moreover, our study demonstrated that miR-596 had other antitumor characteristics, such as inhibiting migration and proliferation. The data from the GEO dataset revealed that the high expression of miR-596 contributed to survival benefits among cancer patients. These results make miR-596 a potential antitumor factor for future biomedical applications.
               
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