ArticleCell death discovery2022
USP15 and USP4 facilitate lung cancer cell proliferation by regulating the alternative splicing of SRSF1.
Article in Cell death discovery, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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The trial behind it
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Who cites it
21 citing papers in PubMed, 20 citations in OpenAlex.
- The Role of Alternative Splicing in Lung Cancer: Mechanisms, Regulators, and Therapeutic Implications.International journal of molecular sciences · 2026Review
- A novel antisense lncRNA, LPCRL, functions as a molecular scaffold for the USP15/MIB1 complex to promote primary cisplatin resistance and tumor progression in lung squamous cell carcinoma.Journal of experimental & clinical cancer research : CR · 2026Article
- Influence of USP15 and its derived-peptide on non-small cell lung cancer immune evasion via regulating PD-L1 stability.Journal for immunotherapy of cancer · 2026Article
- [Expression, Prognostic and Functional Analysis of SRSF Family Proteins in Non-small Cell Lung Cancer].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2026Article
- Pathological role of deubiquitinating enzymes in lung cancer: recent insights and advances.American journal of cancer research · 2026Review
- USP4-Mediated deubiquitination of A2AR suppresses autophagy-dependent ferroptosis in gastric cancer.Cellular and molecular life sciences : CMLS · 2025Article
- Transcriptomic analysis reveals lung cancer and subtype-specific alternative splicing biomarkers regulated by RNA-binding proteins.Molecular therapy. Nucleic acids · 2025Article
- USP15 Drives NSCLC Progression and Chemoresistance, Potentially via Regulation of the U2-Type Spliceosomal Complex.Cancer medicine · 2025Article
- Deubiquitinase USP18 mediates cell migration, apoptosis and ferroptosis in lung adenocarcinoma by depending on POU4F1/PRKAA2 axis.BMC cancer · 2025Article
- The Role of the Dysregulation of circRNAs Expression in Glioblastoma Multiforme.Journal of molecular neuroscience : MN · 2025Review
- Tumor-promoting effect and tumor immunity of SRSFs.Frontiers in cell and developmental biology · 2025Review
- USP4 promotes PTC progression by stabilizing LDHA and activating the MAPK and AKT signaling pathway.Aging · 2024Article
- Circ_0001786 facilitates gefitinib resistance and malignant progression in non-small cell lung cancer via miR-34b-5p/SRSF1.Journal of cardiothoracic surgery · 2024Article
- USP4 promotes the proliferation, migration, and invasion of esophageal squamous cell carcinoma by targeting TAK1.Cell death & disease · 2023Article
- RNA splicing alterations in lung cancer pathogenesis and therapy.Cancer pathogenesis and therapy · 2023Review
- SRSF1 induces glioma progression and has a potential diagnostic application in grading primary glioma.Oncology letters · 2023Article
- The roles of protein ubiquitination in tumorigenesis and targeted drug discovery in lung cancer.Frontiers in endocrinology · 2023Review
- The Role of miR-1183: A Potential Suppressor in Hepatocellular Carcinoma via Regulating Splicing Factor SRSF1.Journal of hepatocellular carcinoma · 2023Article
- USP15 promotes pulmonary vascular remodeling in pulmonary hypertension in a YAP1/TAZ-dependent manner.Experimental & molecular medicine · 2023Article
- Binding of Vialinin A andMolecules (Basel, Switzerland) · 2022Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The deubiquitinating enzyme USP15 is implicated in several human cancers by regulating different cellular processes, including splicing regulation. However, the underlying molecular mechanisms of its functional relevance and the successive roles in enhanced tumorigenesis remain ambiguous. Here, we found that USP15 and its close paralog USP4 are overexpressed and facilitate lung cancer cell proliferation by regulating the alternative splicing of SRSF1. Depletion of USP15 and USP4 impair SRSF1 splicing characterized by the replacement of exon 4 with non-coding intron sequences retained at its C-terminus, resulting in an alternative isoform SRSF1-3. We observed an increased endogenous expression of SRSF1 in lung cancer cells as well, and its overexpression significantly enhanced cancer cell phenotype and rescued the depletion effect of USP15 and USP4. However, the alternatively spliced isoform SRSF1-3 was deficient in such aspects for its premature degradation through nonsense-mediated mRNA decay. The increased USP15 expression contributes to the lung adenocarcinoma (LUAD) development and shows significantly lower disease-specific survival of patients with USP15 alteration. In short, we identified USP15 and USP4 as key regulators of SRSF1 alternative splicing with altered functions, which may represent the novel prognostic biomarker as well as a potential target for LUAD.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.