ArticleMolecular oncology2017
A genome-wide siRNA screen for regulators of tumor suppressor p53 activity in human non-small cell lung cancer cells identifies components of the RNA splicing machinery as targets for anticancer treatment.
Article in Molecular oncology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 71 citations in OpenAlex.
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- Trans-ancestry transcriptome-wide association and functional studies to uncover novel susceptibility genes and therapeutic targets for colorectal cancer.NPJ precision oncology · 2025Article
- The therapeutic potential of circular RNAs.Nature reviews. Genetics · 2025Review
- Interaction of STIL with FOXM1 regulates SF3A3 transcription in the hepatocellular carcinoma development.Cell division · 2025Article
- Bioinformatics analysis across pan-cancer and experimental validation in hepatocellular carcinoma revealed the oncogenic role of SF3B6.Frontiers in pharmacology · 2025Article
- Regulation of HNRNP family by post-translational modifications in cancer.Cell death discovery · 2024Review
- Oncofetal SNRPE promotes HCC tumorigenesis by regulating the FGFR4 expression through alternative splicing.British journal of cancer · 2024Article
- Conserved role of hnRNPL in alternative splicing of epigenetic modifiers enables B cell activation.EMBO reports · 2024Article
- MYCN and SNRPD3 cooperate to maintain a balance of alternative splicing events that drives neuroblastoma progression.Oncogene · 2024Article
- Interpretable meta-learning of multi-omics data for survival analysis and pathway enrichment.Bioinformatics (Oxford, England) · 2023Article
- Evaluation of a Novel Oncolytic Adenovirus SilencingInternational journal of molecular sciences · 2022Article
- CircSCAP interacts with SF3A3 to inhibit the malignance of non-small cell lung cancer by activating p53 signaling.Journal of experimental & clinical cancer research : CR · 2022Article
- Modulation of RNA splicing associated with Wnt signaling pathway using FD-895 and pladienolide B.Aging · 2022Article
- Extracting functional insights from loss-of-function screens using deep link prediction.Cell reports methods · 2022Article
- Article
- Overexpressed SNRPB/D1/D3/E/F/G correlate with poor survival and immune infiltration in hepatocellular carcinoma.American journal of translational research · 2022Article
- SNRPD1/E/F/G Serve as Potential Prognostic Biomarkers in Lung Adenocarcinoma.Frontiers in genetics · 2022Article
- GEMIN6 Overexpression Correlates with the Low Immune Cell Infiltration and Poor Prognosis in Lung Adenocarcinoma.Journal of oncology · 2022Article
- Non-targeting control for MISSION shRNA library silencesMolecular therapy. Nucleic acids · 2021Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Reinstating wild-type tumor suppressor p53 activity could be a valuable option for the treatment of cancer. To contribute to development of new treatment options for non-small cell lung cancer (NSCLC), we performed genome-wide siRNA screens for determinants of p53 activity in NSCLC cells. We identified many genes not previously known to be involved in regulating p53 activity. Silencing p53 pathway inhibitor genes was associated with loss of cell viability. The largest functional gene cluster influencing p53 activity was mRNA splicing. Prominent p53 activation was observed upon silencing of specific spliceosome components, rather than by general inhibition of the spliceosome. Ten genes were validated as inhibitors of p53 activity in multiple NSCLC cell lines: genes encoding the Ras pathway activator SOS1, the zinc finger protein TSHZ3, the mitochondrial membrane protein COX16, and the spliceosome components SNRPD3, SF3A3, SF3B1, SF3B6, XAB2, CWC22, and HNRNPL. Silencing these genes generally increased p53 levels, with distinct effects on CDKN1A expression, induction of cell cycle arrest and cell death. Silencing spliceosome components was associated with alternative splicing of MDM4 mRNA, which could contribute to activation of p53. In addition, silencing splice factors was particularly effective in killing NSCLC cells, albeit in a p53-independent manner. Interestingly, silencing SNRPD3 and SF3A3 exerted much stronger cytotoxicity to NSCLC cells than to lung fibroblasts, suggesting that these genes could represent useful therapeutic targets.
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