PHAROH lncRNA regulates Myc translation in hepatocellular carcinoma via sequestering TIAR

Yu, Allen T, Berasain, Carmen, Bhatia, Sonam, Rivera, Keith, Liu, Bodu, Rigo, Frank, Pappin, Darryl J, Spector, David L (May 2021) PHAROH lncRNA regulates Myc translation in hepatocellular carcinoma via sequestering TIAR. eLife, 10. ISSN 2050-084X

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URL: https://www.ncbi.nlm.nih.gov/pubmed/34002693

DOI: 10.7554/eLife.68263

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.

Item Type:	Paper
Subjects:	diseases & disorders diseases & disorders > neoplasms organs, tissues, organelles, cell types and functions > cell types and functions > cell types > cell line organs, tissues, organelles, cell types and functions > cell types and functions > cell types > cell line organs, tissues, organelles, cell types and functions > cell types and functions > cell types > cell line organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions diseases & disorders > cancer > cancer types > liver cancer organs, tissues, organelles, cell types and functions Investigative techniques and equipment > assays > RNA-seq organs, tissues, organelles, cell types and functions > cell types and functions > cell types > stem cells organs, tissues, organelles, cell types and functions > cell types and functions > cell types > stem cells organs, tissues, organelles, cell types and functions > cell types and functions > cell types > stem cells
CSHL Authors:	Yu, Allen Bhatia, Sonam Rivera, Keith Liu, Bodu Pappin, Darryl J. Spector, David L.
Communities:	CSHL labs > Pappin lab CSHL labs > Spector lab CSHL Cancer Center Program CSHL Cancer Center Program > Gene Regulation and Inheritance Program
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	18 May 2021
Date Deposited:	19 May 2021 18:00
Last Modified:	13 Feb 2024 19:40
PMCID:	PMC8163507
URI:	https://repository.cshl.edu/id/eprint/40091

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