PHAROH lncRNA regulates c-Myc translation in hepatocellular carcinoma via sequestering TIAR

Yu, Allen, Berasain, Carmen, Bhatia, Sonam, Rivera, Keith, Liu, Bodu, Rigo, Frank, Pappin, Darryl, Spector, David (2021) PHAROH lncRNA regulates c-Myc translation in hepatocellular carcinoma via sequestering TIAR. bioRxiv. (Submitted)

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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 c-Myc motif in their promoter. C-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 c-MYC translation. In summary, our data suggest that PHAROH regulates c-MYC translation by sequestering TIAR and as such represents a potentially exciting diagnostic or therapeutic target in hepatocellular carcinoma.

Item Type:	Paper
Subjects:	bioinformatics diseases & disorders > cancer bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification diseases & disorders bioinformatics > genomics and proteomics > genetics & nucleic acid processing bioinformatics > genomics and proteomics diseases & disorders > cancer > cancer types > liver cancer bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > mRNA diseases & disorders > cancer > cancer types
CSHL Authors:	Yu, Allen Bhatia, Sonam Liu, Bodu Pappin, Darryl J. Spector, David L.
Communities:	CSHL labs > Pappin lab CSHL labs > Spector lab
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	2021
Date Deposited:	13 Oct 2023 13:39
Last Modified:	26 Jan 2024 16:44
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/41219

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