ArticleOncogene2016
Therapeutic potential of targeting IRES-dependent c-myc translation in multiple myeloma cells during ER stress.
Article in Oncogene, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 48 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
48 citing papers in PubMed, 68 citations in OpenAlex.
- MYC upstream region orchestrates resistance to PI3K inhibitors in cancer cells through FOXO3a-mediated autophagic adaptation.Oncogene · 2024Article
- Autophagy-related mechanisms for treatment of multiple myeloma.Cancer drug resistance (Alhambra, Calif.) · 2023Review
- Complex CDKL5 translational regulation and its potential role in CDKL5 deficiency disorder.Frontiers in cellular neuroscience · 2023Article
- Long non-coding RNAeLife · 2022Article
- Decoding endoplasmic reticulum stress signals in cancer cells and antitumor immunity.Trends in cancer · 2022Review
- Partners in crime: Proteins implicated in RNA repeat expansion diseases.Wiley interdisciplinary reviews. RNA · 2022Review
- Targeting Oncogene Promoters and Ribosomal RNA Biogenesis by G-Quadruplex Binding Ligands Translate to Anticancer Activity.ACS bio & med chem Au · 2022Article
- Critical Role for Cap-Independent c-MYC Translation in Progression of Multiple Myeloma.Molecular cancer therapeutics · 2022Article
- hnRNP A1 in RNA metabolism regulation and as a potential therapeutic target.Frontiers in pharmacology · 2022Review
- Protein co-expression network-based profiles revealed from laser-microdissected cancerous cells of lung squamous-cell carcinomas.Scientific reports · 2021Article
- Targeting IRES-dependent translation as a novel approach for treating Duchenne muscular dystrophy.RNA biology · 2021Review
- The plasticity of mRNA translation during cancer progression and therapy resistance.Nature reviews. Cancer · 2021Review
- CD46 splice variant enhances translation of specific mRNAs linked to an aggressive tumor cell phenotype in bladder cancer.Molecular therapy. Nucleic acids · 2021Article
- A memory of eS25 loss drives resistance phenotypes.Nucleic acids research · 2020Article
- Regulation of Epithelial-to-Mesenchymal Transition by Alternative Translation Initiation Mechanisms and Its Implications for Cancer Metastasis.International journal of molecular sciences · 2020Review
- MYC and the unfolded protein response in cancer: synthetic lethal partners in crime?EMBO molecular medicine · 2020Review
- Integrated stress response in hepatitis C promotes Nrf2-related chaperone-mediated autophagy: A novel mechanism for host-microbe survival and HCC development in liver cirrhosis.Seminars in cell & developmental biology · 2020Review
- Deeping in the Role of the MAP-Kinases Interacting Kinases (MNKs) in Cancer.International journal of molecular sciences · 2020Review
- Review
- The role of CSDE1 in translational reprogramming and human diseases.Cell communication and signaling : CCS · 2020Review
Corrections and comments
- Retraction · 2023-08-31Concerns/Issues about Data · Concerns/Issues about Image · Duplication of/in Image · Original Data and/or Images not Provided and/or not Available · Unreliable Data · · see also: https://pubpeer.com/publications/7041D5E3ABAF04BC7CB3731371F879 ; Alan Lichtenstein has VA finding of misconduct: see https://www.federalregister.gov/documents/2024/11/18/2024-26756/findings-of-research-misconduct-c;
- Retracted
Authors and funding
7 authors at 1 institution.
Funding
Abstract
Protein translation is inhibited by the unfolded protein response (UPR)-induced eIF-2α phosphorylation to protect against endoplasmic reticulum (ER) stress. In addition, we found additional inhibition of protein translation owing to diminished mTORC1 (mammalian target of rapamycin complex1) activity in ER-stressed multiple myeloma (MM) cells. However, c-myc protein levels and myc translation was maintained. To ascertain how c-myc was maintained, we studied myc IRES (internal ribosome entry site) function, which does not require mTORC1 activity. Myc IRES activity was upregulated in MM cells during ER stress induced by thapsigargin, tunicamycin or the myeloma therapeutic bortezomib. IRES activity was dependent on upstream MAPK (mitogen-activated protein kinase) and MNK1 (MAPK-interacting serine/threonine kinase 1) signaling. A screen identified hnRNP A1 (A1) and RPS25 as IRES-binding trans-acting factors required for ER stress-activated activity. A1 associated with RPS25 during ER stress and this was prevented by an MNK inhibitor. In a proof of principle, we identified a compound that prevented binding of A1 to the myc IRES and specifically inhibited myc IRES activity in MM cells. This compound, when used alone, was not cytotoxic nor did it inhibit myc translation or protein expression. However, when combined with ER stress inducers, especially bortezomib, a remarkable synergistic cytotoxicity ensued with associated inhibition of myc translation and expression. These results underscore the potential for targeting A1-mediated myc IRES activity in MM cells during ER stress.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.