AGO2 Mediates MYC mRNA Stability in Hepatocellular Carcinoma
- 1 April 2020
- journal article
- research article
- Published by American Association for Cancer Research (AACR) in Molecular Cancer Research
- Vol. 18 (4), 612-622
- https://doi.org/10.1158/1541-7786.MCR-19-0805
Abstract
Deregulated RNA-binding proteins (RBP), such as Argonaute 2 (AGO2), mediate tumor-promoting transcriptomic changes during carcinogenesis, including hepatocellular carcinoma (HCC). While AGO2 is well characterized as a member of the RNA-induced silencing complex (RISC), which represses gene expression through miRNAs, its role as a bona fide RBP remains unclear. In this study, we investigated AGO2's role as an RBP that regulates the MYC transcript to promote HCC. Using mRNA and miRNA arrays from patients with HCC, we demonstrate that HCCs with elevated AGO2 levels are more likely to have the mRNA transcriptome deregulated and are associated with poor survival. Moreover, AGO2 overexpression stabilizes the MYC transcript independent of miRNAs. These observations provide a novel mechanism of gene regulation by AGO2 and provide further insights into the potential functions of AGO2 as an RBP in addition to RISC.Other Versions
Funding Information
- Intramural Research Program of the Center for Cancer Research (Z01 BC 010877, Z01 BC 010876)
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