Melixetian et al. 2020 (PRJNA517673)
General Details
| Title | Ribosome profiling analysis of lncRNA TINCR silenced primary melanoma cell line WM902B |
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| Organism | |
| Number of Samples | 4 |
| Release Date | 2019/01/29 00:00 |
| Sequencing Types | |
| Protocol Details |
Study Links
| GWIPS-viz | Trips-Viz |
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Repository Details
| SRA | SRP182817 |
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| ENA | SRP182817 |
| GEO | |
| BioProject | PRJNA517673 |
Publication
| Title | |
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| Authors | Melixetian M,Bossi D,Mihailovich M,Punzi S,Barozzi I,Marocchi F,Cuomo A,Bonaldi T,Testa G,Marine JC,Leucci E,Minucci S,Pelicci PG,Lanfrancone L |
| Journal | EMBO reports |
| Publication Date | 2021 Mar 3 |
| Abstract | Transition from proliferative-to-invasive phenotypes promotes metastasis and therapy resistance in melanoma. Reversion of the invasive phenotype, however, is challenged by the poor understanding of mechanisms underlying its maintenance. Here, we report that the lncRNA TINCR is down-regulated in metastatic melanoma and its silencing increases the expression levels of invasive markers, in vitro migration, in vivo tumor growth, and resistance to BRAF and MEK inhibitors. The critical mediator is ATF4, a central player of the integrated stress response (ISR), which is activated in TINCR-depleted cells in the absence of starvation and eIF2α phosphorylation. TINCR depletion increases global protein synthesis and induces translational reprogramming, leading to increased translation of mRNAs encoding ATF4 and other ISR proteins. Strikingly, re-expression of TINCR in metastatic melanoma suppresses the invasive phenotype, reduces numbers of tumor-initiating cells and metastasis formation, and increases drug sensitivity. Mechanistically, TINCR interacts with mRNAs associated with the invasive phenotype, including ATF4, preventing their binding to ribosomes. Thus, TINCR is a suppressor of the melanoma invasive phenotype, which functions in nutrient-rich conditions by repressing translation of selected ISR RNAs. © 2021 The Authors. Published under the terms of the CC BY NC ND 4.0 license. |
| PMC | PMC7926219 |
| PMID | 33586907 |
| DOI |
| Run Accession | Study Accession | Scientific Name | Cell Line | Library Type | Treatment | GWIPS-viz | Trips-Viz | Reads | BAM | BigWig (F) | BigWig (R) | ||
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| SRR8502838 | PRJNA517673 | Homo sapiens | WM902Bprimary melanoma cell line | Ribo-Seq |  |
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| SRR8502839 | PRJNA517673 | Homo sapiens | WM902Bprimary melanoma cell line | Ribo-Seq | |
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| SRR8502840 | PRJNA517673 | Homo sapiens | WM902Bprimary melanoma cell line | Ribo-Seq | |
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| SRR8502841 | PRJNA517673 | Homo sapiens | WM902Bprimary melanoma cell line | Ribo-Seq | |
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| Run Accession | Study Accession | Scientific Name | Cell Line | Library Type | Treatment | GWIPS-viz | Trips-Viz | Reads | BAM | BigWig (F) | BigWig (R) |
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