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

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.

ORGANISM(S): Mus musculus

PROVIDER: GSE167316 | GEO | 2021/05/09

REPOSITORIES: GEO

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

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

| PRJNA704277 | ENA

Genome-wide analysis of TIAR RNA ligands in mouse macrophages before and after LPS stimulation

2016-02-05 | GSE77577 | GEO

TIAR and FMRP shape pro-survival nascent proteome of leukemia cells in the bone marrow microenvironment

Project description:Chronic myeloid leukemia (CML) cells circulate between blood and bone marrow niche, representing different microenvironments. We studied the role of the two RNA binding proteins, T-cell-restricted intracellular antigen (TIAR) and the fragile X mental retardation protein (FMRP) in the regulation of protein translation in CML cells residing in settings mimicking peripheral blood microenvironment (PBM) and bone marrow microenvironment (BMM). We studied how conditions shaped the translation process through TIAR and FMRP activity, considering its relevance in therapy resistance. The QuaNCAT mass-spectrometric approach revealed that TIAR and FMRP have a discrete modulatory effect on protein synthesis and thus affect distinct aspects of leukemic cells functioning in the hypoxic niche. We demonstrate that TIAR substantially supports the resistance of CML cells to translation inhibition by homoharringtonine in the BMM. Overall, our results show that targeting post-transcriptional control should be considered when designing anti-leukemia therapeutic solutions.

2023-05-10 | PXD032332 | Pride

Genome-wide analysis of TIAR RNA ligands in mouse macrophages before and after LPS stimulation

Project description:TIA-1 related protein (TIAR) is a RNA-binding protein involved in several steps of gene expression such RNA splicing and translation. TIAR contains three RNA recognition motifs (RRMs) allowing its interaction with specific sequences localized in the untranslated regions (UTRs) of several mRNAs. In myeloid cells, TIAR has been shown to bind and regulate the translation and stability of various mRNAs encoding proteins important for the inflammatory response, such as TNFÎ±, Cox-2 or IL-8 . Here, we generated two macrophage-like RAW 264.7 cell lines expressing either a tagged full-length TIAR protein or a RRM2-truncated mutant unable to bind RNA with high affinity . By a combination of RNA-IP and microarray analysis (RIP-chip), we identified mRNAs specifically bound by the full-length protein both in basal conditions and in response to LPS. Microarray hybridization was performed on TIAR-FLAG-associated mRNAs or TIARÎRRM2-FLAG-associated mRNAs in unstimulated and LPS-stimulated RAW264.7 cells. Enrichment of TIAR-FLAG-associated mRNAs and TIARÎRRM2-FLAG-associated mRNAS were normalized to total transcriptome of TIAR-FLAG and TIARÎRRM2-FLAG expressing-RAW264.7 cells respectively. After amplification and labelling, sample pairs were hybridized onto Mouse Exonic Evidence Based Oligonucleotide (MEEBO) arrays containing on average 38784 mouse 70mer oligonucleotide probes (Stanford University, US). Hybridizations were replicated with dye swap.

2016-02-05 | E-GEOD-77577 | biostudies-arrayexpress

TIAR represses c-Myc biosynthesis following ultraviolet light irradiation

Project description:RNA was isolated from material that had been subjected to immunoprecipitation (IP) from RKO cells that were either left untreated or irradiated with 20 J/m2 UVC and collected 1h later; IP assays were carried out using either an antibody recognizing RNA-binding protein TIAR, or using a control IgG1 antibody. RNA was reverse-transcribed in the presence of [alpha-33P]dCTP and the radiolabeled product used to hybridize human cDNA arrays. The experiment was repeated using three independent sample sets. The samples were numbered Tc-1, Tc-2, Tc-3, Tuv-1, Tuv-2, Tuv-3, IgG1c-1, IgG1c-2, IgG1c-3, IgG1uv-1, IgG1uv-2, and IgG1uv-3. ‘Tc’ denotes RNA from IP reactions using untreated cells and anti-TIAR antibody, ‘Tuv’ denotes RNA from IP reactions using UVC-treated cells and anti-TIAR antibody, ‘IgG1c’ denotes RNA from IP reactions using untreated cells and anti-IgG1 antibody, and ‘IgG1uv’ denotes RNA from IP reactions using UVC-treated cells and anti-IgG1 antibody. The numbers 1, 2 and 3 correspond to the three independent experimental datasets. Keywords = post-transcriptional / translation / nascent protein synthesis / stress response / ribonomics Keywords: ordered

2004-05-27 | GSE1433 | GEO

TIAR represses c-Myc biosynthesis following ultraviolet light irradiation

Project description:RNA was isolated from material that had been subjected to immunoprecipitation (IP) from RKO cells that were either left untreated or irradiated with 20 J/m2 UVC and collected 1h later; IP assays were carried out using either an antibody recognizing RNA-binding protein TIAR, or using a control IgG1 antibody. RNA was reverse-transcribed in the presence of [alpha-33P]dCTP and the radiolabeled product used to hybridize human cDNA arrays. The experiment was repeated using three independent sample sets. The samples were numbered Tc-1, Tc-2, Tc-3, Tuv-1, Tuv-2, Tuv-3, IgG1c-1, IgG1c-2, IgG1c-3, IgG1uv-1, IgG1uv-2, and IgG1uv-3. âTcâ denotes RNA from IP reactions using untreated cells and anti-TIAR antibody, âTuvâ denotes RNA from IP reactions using UVC-treated cells and anti-TIAR antibody, âIgG1câ denotes RNA from IP reactions using untreated cells and anti-IgG1 antibody, and âIgG1uvâ denotes RNA from IP reactions using UVC-treated cells and anti-IgG1 antibody. The numbers 1, 2 and 3 correspond to the three independent experimental datasets. Keywords = post-transcriptional / translation / nascent protein synthesis / stress response / ribonomics Keywords: ordered

2010-06-09 | E-GEOD-1433 | biostudies-arrayexpress

LncRNA MT1JP Interacts with TIAR to Modulate p53 pathway during Tumorigenesis

Project description:Long non-coding RNAs (lncRNAs) are best known for playing diverse roles at transcriptional level. Here we report a lncRNA MT1JP for its posttranscriptional function as a modulator of tumorigenesis. By associating with RNA-binding protein TIAR, MT1JP favored the translation of vital transcription factor p53, and then regulated a series of p53 involved pathways such as cell cycle, apoptosis, proliferation and so forth. With down-regulation of MT1JP, the protein level of p53 was declined, which in turn accelerated cell deteriorate and tumor formation. Moreover, differential expression of MT1JP in tumor tissues and matched normal tissues suggests that it may be an excellent prognosis and therapy target as a tumor suppressor. Together, our finding identifies MT1JP as a critical lncRNA required for restraining tumorigenesis, which occurs through MT1JP interacting with TIAR to modulate p53 translation.

2018-06-15 | GSE69870 | GEO

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2022-03-07 | GSE197915 | GEO

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2022-10-12 | PXD031478 | Pride