ArticleEBioMedicine2020
Dysregulation of the splicing machinery is directly associated to aggressiveness of prostate cancer.
Article in EBioMedicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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Who cites it
67 citing papers in PubMed, 111 citations in OpenAlex.
- Modulation of inflammasome components in patients with heart failure using oral nutritional supplements: investigating the molecular mechanisms beyond the clinical benefit.European journal of nutrition · 2026Trial
- The role of splicing factor SRSF3 in cancer progression: Mechanisms, biomarkers, and therapeutic implications.Translational oncology · 2026Review
- Intermittent time-restricted feeding recapitulates the physiological benefits of daily time-restricted feeding in male mice with chronic metabolic disease.Molecular metabolism · 2026Article
- Article
- An Integrative RNA Spliceosomic Landscape of Pancreatic Neuroendocrine Tumors Identifies Clinically Relevant Molecular Subgroups.Endocrine pathology · 2026Article
- Prognostic alternative mRNA splicing signature and immune infiltration in prostate cancer.Journal of applied genetics · 2026Article
- Periprostatic adipose tissue-derived adipokine profile in prostate cancer patients reveals two distinct molecular phenotypes linked to obesity-related comorbidities: multifaceted role of lipocalin-2.Cell communication and signaling : CCS · 2026Article
- Combining ferroptosis inducers with gemcitabine to enhance treatment efficacy in pancreatic cancer.Cancer & metabolism · 2026Article
- Splicing factor TRA2B enhances synthesis of androgen receptor variant AR-V7 in prostate cancer cells.The Journal of clinical investigation · 2026Article
- Molecular background of Philadelphia chromosome dependent enhancement of cellular growth and tyrosine kinase inhibitor sensitivity.Experimental hematology & oncology · 2026Article
- Heterozygous loss of SRRM1 may be associated with neurodevelopmental phenotypes and anomalies in cell growth and neurite morphology.European journal of human genetics : EJHG · 2026Article
- Lactate derived from cancer-associated fibroblasts promotes alternative splicing and castration resistance in prostate cancer.Science advances · 2026Article
- Systematic investigation of zinc finger MYND-type containing 11-mediated alternative splicing reveals notable events in prostate cancer.Asian journal of urology · 2026Article
- MiR-7 inhibits progression of glioblastoma by impairing autophagy resolution, energy metabolism and ECM remodeling.Journal of experimental & clinical cancer research : CR · 2025Article
- Screening and validation of key genes involved in castration-resistant prostate cancer based on transcriptomics sequencing.Scientific reports · 2025Article
- Impaired splicing machinery in craniopharyngiomas unveils PRPF8 and RAVER1 as novel biomarkers and therapeutic targets.Acta neuropathologica communications · 2025Article
- Targeting the CLK2/SRSF9 splicing axis in prostate cancer leads to decreased ARV7 expression.Molecular oncology · 2025Article
- The splicing machinery is dysregulated and represents a therapeutic vulnerability in breast cancer.Cellular and molecular life sciences : CMLS · 2024Article
- Clinical value of circulating splicing factors in prostate cancer: SRRM1 as a novel predictive biomarker and therapeutic target.Molecular therapy. Oncology · 2024Article
- SRSF6 modulates histone-chaperone HIRA splicing to orchestrate AR and E2F activity in prostate cancer.Science advances · 2024Article
7 more citing papers are in PubMed but not listed here.
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Authors and funding
19 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDysregulation of splicing variants (SVs) expression has recently emerged as a novel cancer hallmark. Although the generation of aberrant SVs (e.g. AR-v7/sst5TMD4/etc.) is associated to prostate-cancer (PCa) aggressiveness and/or castration-resistant PCa (CRPC) development, whether the molecular reason behind such phenomena might be linked to a dysregulation of the cellular machinery responsible for the splicing process [spliceosome-components (SCs) and splicing-factors (SFs)] has not been yet explored.
methodsExpression levels of 43 key SCs and SFs were measured in two cohorts of PCa-samples: 1) Clinically-localized formalin-fixed paraffin-embedded PCa-samples (n = 84), and 2) highly-aggressive freshly-obtained PCa-samples (n = 42).
findingsA profound dysregulation in the expression of multiple components of the splicing machinery (i.e. 7 SCs/19 SFs) were found in PCa compared to their non-tumor adjacent-regions. Notably, overexpression of SNRNP200, SRSF3 and SRRM1 (mRNA and/or protein) were associated with relevant clinical (e.g. Gleason score, T-Stage, metastasis, biochemical recurrence, etc.) and molecular (e.g. AR-v7 expression) parameters of aggressiveness in PCa-samples. Functional (cell-proliferation/migration) and mechanistic [gene-expression (qPCR) and protein-levels (western-blot)] assays were performed in normal prostate cells (PNT2) and PCa-cells (LNCaP/22Rv1/PC-3/DU145 cell-lines) in response to SNRNP200, SRSF3 and/or SRRM1 silencing (using specific siRNAs) revealed an overall decrease in proliferation/migration-rate in PCa-cells through the modulation of key oncogenic SVs expression levels (e.g. AR-v7/PKM2/XBP1s) and alteration of oncogenic signaling pathways (e.g. p-AKT/p-JNK).
interpretationThese results demonstrate that the spliceosome is drastically altered in PCa wherein SNRNP200, SRSF3 and SRRM1 could represent attractive novel diagnostic/prognostic and therapeutic targets for PCa and CRPC.
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