ArticleGenome medicine2018
Therapy-induced stress response is associated with downregulation of pre-mRNA splicing in cancer cells.
Article in Genome medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 35 citations in OpenAlex.
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- The Transgenerational Impact of High-Fat Diet and Diabetic Pregnancy on Embryonic Transcriptomics and Mitochondrial Health.Biomedicines · 2025Article
- Splicing inhibition mediated by reduced splicing factors and helicases is associated with the cellular response of lung cancer cells to cisplatin.Computational and structural biotechnology journal · 2024Article
- Splicing modulators impair DNA damage response and induce killing of cohesin-mutant MDS and AML.Science translational medicine · 2024Article
- Remodeling of the chromatin landscape in peripheral blood cells in patients with severe Delta COVID-19.Frontiers in immunology · 2024Article
- Data-Independent Acquisition Mass Spectrometry Analysis of FFPE Rectal Cancer Samples Offers In-Depth Proteomics Characterization of the Response to Neoadjuvant Chemoradiotherapy.International journal of molecular sciences · 2023Article
- Aberrant DNA Methylation, Expression, and Occurrence of Transcript Variants of the ABC TransporterCells · 2023Article
- Stress-Inducible SCAND Factors Suppress the Stress Response and Are Biomarkers for Enhanced Prognosis in Cancers.International journal of molecular sciences · 2023Article
- The transcription factor c-Jun inhibits RBM39 to reprogram pre-mRNA splicing during genotoxic stress.Nucleic acids research · 2022Article
- Alternative RNA splicing modulates ribosomal composition and determines the spatial phenotype of glioblastoma cells.Nature cell biology · 2022Article
- Highly Sensitive Nanomagnetic Quantification of Extracellular Vesicles by Immunochromatographic Strips: A Tool for Liquid Biopsy.Nanomaterials (Basel, Switzerland) · 2022Article
- Hereditary retinoblastoma iPSC model reveals aberrant spliceosome function driving bone malignancies.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- The Prognostic Significance of Spliceosomal Proteins for Patients with Glioblastoma.Doklady. Biochemistry and biophysics · 2022Article
- Alternative Splicing in Myeloid Malignancies.Biomedicines · 2021Review
- Proteomic Analysis of Marinesco-Sjogren Syndrome Fibroblasts Indicates Pro-Survival Metabolic Adaptation to SIL1 Loss.International journal of molecular sciences · 2021Article
- Intermittent leucine pulses during continuous feeding alters novel components involved in skeletal muscle growth of neonatal pigs.Amino acids · 2020Article
- ΔNp63 drives epithelial differentiation in glioma.Clinical and translational medicine · 2020Article
- Hypoxia-induced alternative splicing: the 11th Hallmark of Cancer.Journal of experimental & clinical cancer research : CR · 2020Review
- Muscleblind-like 2 controls the hypoxia response of cancer cells.RNA (New York, N.Y.) · 2020Article
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundAbnormal pre-mRNA splicing regulation is common in cancer, but the effects of chemotherapy on this process remain unclear.
methodsTo evaluate the effect of chemotherapy on slicing regulation, we performed meta-analyses of previously published transcriptomic, proteomic, phosphoproteomic, and secretome datasets. Our findings were verified by LC-MS/MS, western blotting, immunofluorescence, and FACS analyses of multiple cancer cell lines treated with cisplatin and pladienolide B.
resultsOur results revealed that different types of chemotherapy lead to similar changes in alternative splicing by inducing intron retention in multiple genes. To determine the mechanism underlying this effect, we analyzed gene expression in 101 cell lines affected by ɣ-irradiation, hypoxia, and 10 various chemotherapeutic drugs. Strikingly, оnly genes involved in the cell cycle and pre-mRNA splicing regulation were changed in a similar manner in all 335 tested samples regardless of stress stimuli. We revealed significant downregulation of gene expression levels in these two pathways, which could be explained by the observed decrease in splicing efficiency and global intron retention. We showed that the levels of active spliceosomal proteins might be further post-translationally decreased by phosphorylation and export into the extracellular space. To further explore these bioinformatics findings, we performed proteomic analysis of cisplatin-treated ovarian cancer cells. Finally, we demonstrated that the splicing inhibitor pladienolide B impairs the cellular response to DNA damage and significantly increases the sensitivity of cancer cells to chemotherapy.
conclusionsDecreased splicing efficiency and global intron retention is a novel stress response mechanism that may promote survival of malignant cells following therapy. We found that this mechanism can be inhibited by pladienolide B, which significantly increases the sensitivity of cancer cells to cisplatin which makes it a good candidate drug for improving the efficiency of cancer therapy.
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