High-Throughput Identification of miR-596 Inducing p53-Mediated Apoptosis in HeLa and HCT116 Cells Using Cell Microarray. (December 2017)

• Record Type: Journal Article
• Authors: Ma, Ming; Yang, Junyu; Wang, Bolun; Zhao, Zhihua; Xi, Jianzhong Jeff
• Is Part Of: SLAS technology. Volume 22:Number 6(2017)
• Page Start: 636
• Page End: 645
• Publication Date: 2017-12
• Subjects: high-content screening -- miR-596 -- apoptosis -- p53; Medical laboratory technology -- Periodicals; Laboratories -- Equipment and supplies -- Periodicals; Diagnosis, Laboratory -- Periodicals; 616.075
• DOI: 10.1177/2472630317720870
• Languages: English
• ISSNs: 2472-6303

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.