Authors: | Brockway, S.; Zeleznik-Le, N. J. |
Article Title: | WEE1 is a validated target of the microRNA miR-17-92 cluster in leukemia |
Abstract: | MicroRNAs are short single-stranded RNAs that regulate target gene expression by binding to complementary sites in the 3' untranslated region (UTR) of their mRNA targets. The polycistronic miR-17-92 cluster, which encodes miR-17, miR-18a, miR-19a, miR-20a, miR-19b, and miR-92a, was previously shown to be overexpressed in multiple types of cancer. In this study, target gene prediction algorithms were used to predict potential targets of the miR-17-92 cluster. WEE1, a kinase that inhibits cell cycle progression, was identified as a possible target of five of the six miRNAs in the cluster. Luciferase reporter assays were used to determine that miR-17, miR-20a, and miR-18a specifically target nucleotides 465-487 of the 3' UTR of WEE1, whereas miR-19a and miR-19b exert control on WEE1 by targeting nucleotides 1069-1091. A negative correlation was determined between endogenous miR-17 or miR-19a expression and endogenous WEE1 protein expression in the same panel of cell lines. We conclude that WEE1 is a valid target of the miR-17-92 cluster in leukemia. |
Journal Title: | Cancer genetics |
Volume: | 208 |
Issue: | 5 |
ISSN: | 2210-7762 |
Publisher: | Elsevier Inc |
Date Published: | 2015 |
Start Page: | 279 |
End Page: | 287 |
Language: | ENG |
DOI/URL: |
S2210-7762(15)00002-2 |
Notes: | LR: 20150323; CI: Copyright (c) 2015; GR: R01 HL087188/HL/NHLBI NIH HHS/United States; JID: 101539150; OTO: NOTNLM; 2014/09/09 [received]; 2015/01/04 [revised]; 2015/01/11 [accepted]; aheadofprint |