PHAROH lncRNA regulates Myc translation in hepatocellular carcinoma via sequestering TIAR
- Cold Spring Harbor Laboratory, United States
- University of Navarra, Spain
- Ionis Pharmaceutials, United States
Abstract
Hepatocellular carcinoma, the most common type of liver malignancy, is one of the most lethal forms of cancer. We identified a long non-coding RNA, Gm19705, that is over-expressed in hepatocellular carcinoma and mouse embryonic stem cells. We named this RNA Pluripotency and Hepatocyte Associated RNA Overexpressed in HCC, or PHAROH. Depletion of PHAROH impacts cell proliferation and migration, which can be rescued by ectopic expression of PHAROH. RNA-seq analysis of PHAROH knockouts revealed that a large number of genes with decreased expression contain a Myc motif in their promoter. MYC is decreased at the protein level, but not the mRNA level. RNA-antisense pulldown identified nucleolysin TIAR, a translational repressor, to bind to a 71-nt hairpin within PHAROH, sequestration of which increases MYC translation. In summary, our data suggest that PHAROH regulates MYC translation by sequestering TIAR and as such represents a potentially exciting diagnostic or therapeutic target in hepatocellular carcinoma.
Data availability
RNA-seq data has been uploaded to GEO: GSE167316
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PHAROH lncRNA regulates c-Myc translation in hepatocellular carcinoma via sequestering TIARNCBI Gene Expression Omnibus, GSE167316.
Article and author information
Author details
Funding
National Cancer Institute (5PO1CA013106-Project 3)
- David L Spector
National Cancer Institute (5F31CA220997)
- Allen T Yu
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: Animal experimental protocols were approved (CEEA 062-16) and performed according to the guidelines of the Ethics Committee for Animal Testing of the University of Navarra.
Human subjects: The Human Research Review Committee of the University of Navarra (CEI 47/2015) approved the study and human samples were provided by the Biobank of the University of Navarra. The biobank obtained an informed consent and consent to publish from each patient and codified samples were provided to the researchers. The study protocol conformed to the ethical guidelines of the 1975 Declaration of Helsinki. Samples were processed following standard operating procedures approved by the Ethical and Scientific Committees. Liver samples from healthy patients were collected from individuals with normal or minimal changes in the liver at surgery of digestive tumors or from percutaneous liver biopsy performed because of mild alterations of liver function. Samples for cirrhotic liver and HCC were obtained from patients undergoing partial hepatectomy and/or liver transplantation.
Copyright
© 2021, Yu et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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PHAROH lncRNA regulates Myc translation in hepatocellular carcinoma via sequestering TIAR
eLife 10:e68263.
https://doi.org/10.7554/eLife.68263
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