<i>PHAROH</i> lncRNA regulates Myc translation in hepatocellular carcinoma via sequestering TIAR.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 34002693.
- Also identified by DOI 10.7554/eLife.68263 and PMC identifier 8163507.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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, <i>Gm19705</i>, that is overexpressed in hepatocellular carcinoma and mouse embryonic stem cells. We named this RNA <i><u>P</u>luripotency and <u>H</u>epatocyte <u>A</u>ssociated <u>R</u>NA <u>O</u>verexpressed in <u>H</u>CC</i>, or <i>PHAROH</i>. Depletion of <i>PHAROH</i> impacts cell proliferation and migration, which can be rescued by ectopic expression of <i>PHAROH</i>. RNA-seq analysis of <i>PHAROH</i> knockouts revealed that a large number of genes with decreased expression contain a <i>Myc</i> motif in their promoter. MYC is decreased in knockout cells 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 <i>PHAROH</i>, sequestration of which increases MYC translation. In summary, our data suggest that <i>PHAROH</i> regulates MYC translation by sequestering TIAR and as such represents a potentially exciting diagnostic or therapeutic target in hepatocellular carcinoma.
Medical subject headings
- Carcinoma, Hepatocellular
- Liver Neoplasms
- Proto-Oncogene Proteins c-myc
- RNA, Long Noncoding
- RNA-Binding Proteins