ArticlePloS one2013
Targeting eukaryotic translation in mesothelioma cells with an eIF4E-specific antisense oligonucleotide.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 35 citations in OpenAlex.
- Therapeutic potential of synthetic microRNA mimics based on the miR-15/107 consensus sequence.Cancer gene therapy · 2025Article
- Biological functions and research progress of eIF4E.Frontiers in oncology · 2023Review
- The dark side of mRNA translation and the translation machinery in glioblastoma.Frontiers in cell and developmental biology · 2023Review
- Control of the eIF4E activity: structural insights and pharmacological implications.Cellular and molecular life sciences : CMLS · 2021Review
- Translation Initiation Machinery as a Tumor Selective Target for Radiosensitization.International journal of molecular sciences · 2021Review
- Inhibitory effects of Tomivosertib in acute myeloid leukemia.Oncotarget · 2021Article
- Repression of oncogenic cap-mediated translation by 4Ei-10 diminishes proliferation, enhances chemosensitivity and alters expression of malignancy-related proteins in mesothelioma.Cancer chemotherapy and pharmacology · 2020Article
- eIF4E Overexpression Is Associated with Poor Prognoses of Ovarian Cancer.Analytical cellular pathology (Amsterdam) · 2020Article
- A Polysome-Based microRNA Screen Identifies miR-24-3p as a Novel Promigratory miRNA in Mesothelioma.Cancer research · 2018Article
- Targeting BRD4 proteins suppresses the growth of NSCLC through downregulation of eIF4E expression.Cancer biology & therapy · 2018Article
- Cap-dependent translational control of oncolytic measles virus infection in malignant mesothelioma.Oncotarget · 2017Article
- Targeting eukaryotic protein translation in mesothelioma.Translational lung cancer research · 2017Review
- Phosphorylation of eIF4E serine 209 is associated with tumour progression and reduced survival in malignant melanoma.British journal of cancer · 2016Article
- Role of Eukaryotic Initiation Factors during Cellular Stress and Cancer Progression.Journal of nucleic acids · 2016Review
- mTOR inhibitors in cancer therapy.F1000Research · 2016Review
- Knockdown of eukaryotic translation initiation factor 4E suppresses cell growth and invasion, and induces apoptosis and cell cycle arrest in a human lung adenocarcinoma cell line.Molecular medicine reports · 2015Article
- Antisense oligonucleotide targeting eukaryotic translation initiation factor 4E reduces growth and enhances chemosensitivity of non-small-cell lung cancer cells.Cancer gene therapy · 2015Article
- Small-molecule inhibition of oncogenic eukaryotic protein translation in mesothelioma cells.Investigational new drugs · 2014Article
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAberrant cap-dependent translation is implicated in tumorigenesis in multiple tumor types including mesothelioma. In this study, disabling the eIF4F complex by targeting eIF4E with eIF4E-specific antisense oligonucleotide (4EASO) is assessed as a therapy for mesothelioma.
methodsMesothelioma cells were transfected with 4EASO, designed to target eIF4E mRNA, or mismatch-ASO control. Cell survival was measured in mesothelioma treated with 4EASO alone or combined with either gemcitabine or pemetrexed. Levels of eIF4E, ODC, Bcl-2 and β-actin were assessed following treatment. Binding to a synthetic cap-analogue was used to study the strength of eIF4F complex activation following treatment.
resultseIF4E level and the formation of eIF4F cap-complex decreased in response to 4EASO, but not mismatch control ASO, resulting in cleavage of PARP indicating apoptosis. 4EASO treatment resulted in dose dependent decrease in eIF4E levels, which corresponded to cytotoxicity of mesothelioma cells. 4EASO resulted in decreased levels of eIF4E in non-malignant LP9 cells, but this did not correspond to increased cytotoxicity. Proteins thought to be regulated by cap-dependent translation, Bcl-2 and ODC, were decreased upon treatment with 4EASO. Combination therapy of 4EASO with pemetrexed or gemcitabine further reduced cell number.
conclusion4EASO is a novel drug that causes apoptosis and selectively reduces eIF4E levels, eIF4F complex formation, and proliferation of mesothelioma cells. eIF4E knockdown results in decreased expression of anti-apoptotic and pro-growth proteins and enhances chemosensitivity.
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