PHAROH lncRNA regulates Myc translation in hepatocellular carcinoma via sequestering TIAR
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 overexpressed in hepatocellular carcinoma and mouse embryonic stem cells. We named this RNA Pluripotency and Hepatocyte Associated RNA...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2021-05-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/68263 |
| _version_ | 1828166639861891072 |
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| author | Allen T Yu Carmen Berasain Sonam Bhatia Keith Rivera Bodu Liu Frank Rigo Darryl J Pappin David L Spector |
| author_facet | Allen T Yu Carmen Berasain Sonam Bhatia Keith Rivera Bodu Liu Frank Rigo Darryl J Pappin David L Spector |
| author_sort | Allen T Yu |
| collection | DOAJ |
| description | 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 overexpressed 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 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 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. |
| first_indexed | 2024-04-12T02:05:43Z |
| format | Article |
| id | doaj.art-72f24e0d4ca04037b061615c66b60f36 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T02:05:43Z |
| publishDate | 2021-05-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-72f24e0d4ca04037b061615c66b60f362022-12-22T03:52:33ZengeLife Sciences Publications LtdeLife2050-084X2021-05-011010.7554/eLife.68263PHAROH lncRNA regulates Myc translation in hepatocellular carcinoma via sequestering TIARAllen T Yu0https://orcid.org/0000-0002-1842-857XCarmen Berasain1Sonam Bhatia2https://orcid.org/0000-0002-0124-2621Keith Rivera3Bodu Liu4Frank Rigo5Darryl J Pappin6David L Spector7https://orcid.org/0000-0003-3614-4965Cold Spring Harbor Laboratory, Cold Spring Harbor, United States; Genetics Program, Stony Brook University, Stony Brook, United StatesHepatology Program, Cima, University of Navarra, Pamplona, Spain; Instituto de Investigaciones Sanitarias de Navarra-IdiSNA, Pamplona, Spain; CIBERehd, Instituto de Salud Carlos III, Madrid, SpainCold Spring Harbor Laboratory, Cold Spring Harbor, United StatesCold Spring Harbor Laboratory, Cold Spring Harbor, United StatesCold Spring Harbor Laboratory, Cold Spring Harbor, United StatesIonis Pharmaceuticals, Carlsbad, United StatesCold Spring Harbor Laboratory, Cold Spring Harbor, United StatesCold Spring Harbor Laboratory, Cold Spring Harbor, United States; Genetics Program, Stony Brook University, Stony Brook, United StatesHepatocellular 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 overexpressed 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 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 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.https://elifesciences.org/articles/68263lncRNATIARhepatocellular carcinoma |
| spellingShingle | Allen T Yu Carmen Berasain Sonam Bhatia Keith Rivera Bodu Liu Frank Rigo Darryl J Pappin David L Spector PHAROH lncRNA regulates Myc translation in hepatocellular carcinoma via sequestering TIAR eLife lncRNA TIAR hepatocellular carcinoma |
| title | PHAROH lncRNA regulates Myc translation in hepatocellular carcinoma via sequestering TIAR |
| title_full | PHAROH lncRNA regulates Myc translation in hepatocellular carcinoma via sequestering TIAR |
| title_fullStr | PHAROH lncRNA regulates Myc translation in hepatocellular carcinoma via sequestering TIAR |
| title_full_unstemmed | PHAROH lncRNA regulates Myc translation in hepatocellular carcinoma via sequestering TIAR |
| title_short | PHAROH lncRNA regulates Myc translation in hepatocellular carcinoma via sequestering TIAR |
| title_sort | pharoh lncrna regulates myc translation in hepatocellular carcinoma via sequestering tiar |
| topic | lncRNA TIAR hepatocellular carcinoma |
| url | https://elifesciences.org/articles/68263 |
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