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:
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:
URI: https://repository.cshl.edu/id/eprint/41219

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