Date of Award

2011

Degree Type

Thesis

Degree Name

Master of Science (MS)

Department

Molecular Biology

Abstract

MicroRNAs are noncoding RNAs that bind to the 3' untranslated region of their mRNA targets, which causes downregulation of target gene expression. Previous studies have shown that the miR-17-92 cluster, which encodes six miRNAs, is overexpressed in leukemias arising from chromosomal translocations of the Mixed Lineage Leukemia (MLL) gene. In the present study, prediction algorithms identified WEE1, a kinase that inhibits cell cycle progression, as a possible target of five of the six miRNAs. Through luciferase reporter assays, we found that miR-17, miR-20a, and miR-18a specifically target nucleotides 465 to 487 of the 3' UTR of WEE1, while miR-19a and miR-19b target nucleotides 1069 to 1091. Notably, while we did not detect a relationship between MLL rearrangement status and miR-17-92 expression in the leukemia cell lines tested, we observed a negative correlation between endogenous miR-17-92 and endogenous WEE1. These results suggest that WEE1 is a target of the miR-17-92 cluster.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.

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