ArticleInternational journal of molecular sciences2020
Silencing Core Spliceosome Sm Gene Expression Induces a Cytotoxic Splicing Switch in the Proteasome Subunit Beta 3 mRNA in Non-Small Cell Lung Cancer Cells.
Article in International journal of molecular sciences, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 17 citations in OpenAlex.
- Integrated genome-wide high-throughput screening and functional validation identifies Sm proteins as essential splicing regulators for gastric cancer progression.Functional & integrative genomics · 2026Article
- Evaluation of Spliceosome Protein SmD2 as a Potential Target for Cancer Therapy.International journal of molecular sciences · 2024Article
- Clinically relevant stratification of lung squamous carcinoma patients based on ubiquitinated proteasome genes for 3P medical approach.The EPMA journal · 2024Article
- MYCN and SNRPD3 cooperate to maintain a balance of alternative splicing events that drives neuroblastoma progression.Oncogene · 2024Article
- Identification of Three Genes Associated with Metastasis in Melanoma and Construction of a Predictive Model: A Multiracial Identification.Journal of oncology · 2022Article
- Bioinformatic Analysis Identifying PSMB 1/2/3/4/6/8/9/10 as Prognostic Indicators in Clear Cell Renal Cell Carcinoma.International journal of medical sciences · 2022Article
- GEMIN6 Overexpression Correlates with the Low Immune Cell Infiltration and Poor Prognosis in Lung Adenocarcinoma.Journal of oncology · 2022Article
- Significance of Spliceosome-Related Genes in the Prediction of Prognosis and Treatment Strategies for Lung Adenocarcinoma.BioMed research international · 2022Article
- SNRPD1/E/F/G Serve as Potential Prognostic Biomarkers in Lung Adenocarcinoma.Frontiers in genetics · 2022Article
- Non-targeting control for MISSION shRNA library silencesMolecular therapy. Nucleic acids · 2021Article
- The Sm core components of small nuclear ribonucleoproteins promote homologous recombination repair.DNA repair · 2021Article
- Biology of the mRNA Splicing Machinery and Its Dysregulation in Cancer Providing Therapeutic Opportunities.International journal of molecular sciences · 2021Review
- The Silence of PSMC6 Inhibits Cell Growth and Metastasis in Lung Adenocarcinoma.BioMed research international · 2021Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The core spliceosomal Sm proteins were recently proposed as cancer-selective lethal targets in non-small cell lung cancer (NSCLC). In contrast, the loss of the commonly mutated cancer target SF3B1 appeared to be toxic to non-malignant cells as well. In the current study, the transcriptomes of A549 NSCLC cells, in which SF3B1 or SNRPD3 was silenced, were compared using RNA sequencing. The skipping of exon 4 of the proteasomal subunit beta type-3 (PSMB3) mRNA, resulting in a shorter PSMB3-S variant, occurred only after silencing SNRPD3. This observation was extended to the other six Sm genes. Remarkably, the alternative splicing of PSMB3 mRNA upon Sm gene silencing was not observed in non-malignant IMR-90 lung fibroblasts. Furthermore, PSMB3 was found to be overexpressed in NSCLC clinical samples and PSMB3 expression correlated with Sm gene expression. Moreover, a high PSMB3 expression corresponds to worse survival in patients with lung adenocarcinomas. Finally, silencing the canonical full-length PSMB3-L, but not the shorter PSMB3-S variant, was cytotoxic and was accompanied by a decrease in proteasomal activity. Together, silencing Sm genes, but not SF3B1, causes a cytotoxic alternative splicing switch in the PSMB3 mRNA in NSCLC cells only.
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