ArticleSignal transduction and targeted therapy2021
SRSF1 inhibits autophagy through regulating Bcl-x splicing and interacting with PIK3C3 in lung cancer.
Article in Signal transduction and targeted therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
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Who cites it
69 citing papers in PubMed, 128 citations in OpenAlex.
- Review
- RNA splicing in cancer cell death regulation: shedding light on the molecular mechanisms and potential clinical applications.Cell death & disease · 2026Review
- CD33 Isoform Splicing Dysregulation: A Molecular Determinant of Microglial Dysfunction in Alzheimer's Disease Pathology.Molecular neurobiology · 2026Review
- ZBED6-IGF2-PIK3C3 autophagy axis drives ccRCC progression: A multi-omics integration study.iScience · 2026Article
- Targeting RNA binding proteins with small-molecule inhibitors: Advances, challenges, and therapeutic opportunities.Acta pharmaceutica Sinica. B · 2026Review
- BCL-2 and BCL-xL in Cancer: Regulation, Function, and Therapeutic Targeting.International journal of molecular sciences · 2026Review
- Silencing serine/arginine-rich splicing factor 1 to induce apoptosis and autophagy-dependent cell death in cholangiocarcinoma through the correction of oncogenic splicing errors.Anatomy & cell biology · 2025Article
- Identification and functional characterization of splicing factors implicated in mantle cell lymphoma aggressiveness.Scientific reports · 2025Article
- Article
- Long non-coding RNA AFAP1-AS1 promotes alternative splicing of AXIN2 by facilitating SRSFs phase separation to induce drug resistance in lung adenocarcinoma.Molecular cancer · 2025Article
- Transcriptomic analysis reveals lung cancer and subtype-specific alternative splicing biomarkers regulated by RNA-binding proteins.Molecular therapy. Nucleic acids · 2025Article
- LncRNA BBOX1-AS1 Contributes to Laryngeal Carcinoma Progression by Recruiting SRSF1 to Maintain EFNB2 mRNA Stability.Biochemical genetics · 2025Article
- Syntaxin-6 mediated autophagy confers lenvatinib resistance in hepatocellular carcinoma.Oncogene · 2025Article
- MRAS: Master Regulator Analysis of Alternative Splicing.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Splicing to keep splicing: A feedback system for cellular homeostasis and state transition.Clinical and translational medicine · 2025Review
- RNA splicing: Novel star in pulmonary diseases with a treatment perspective.Acta pharmaceutica Sinica. B · 2025Review
- RNA-binding proteins and autophagy in lung cancer: mechanistic insights and therapeutic perspectives.Discover oncology · 2025Review
- Glucocorticoids regulate the expression of Srsf1 through Hdac4/Foxc1 axis to induce apoptosis of osteoblasts.Communications biology · 2025Article
- Targeting RNA splicing modulation: new perspectives for anticancer strategy?Journal of experimental & clinical cancer research : CR · 2025Review
- Targeting SRSF1 improves cancer immunotherapy by dually acting on CD8Signal transduction and targeted therapy · 2025Article
9 more citing papers are in PubMed but not listed here.
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Authors and funding
16 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Alternative splicing is a critical process to generate protein diversity. However, whether and how alternative splicing regulates autophagy remains largely elusive. Here we systematically identify the splicing factor SRSF1 as an autophagy suppressor. Specifically, SRSF1 inhibits autophagosome formation by reducing the accumulation of LC3-II and numbers of autophagosomes in different cell lines. Mechanistically, SRSF1 promotes the splicing of the long isoform of Bcl-x that interacts with Beclin1, thereby dissociating the Beclin1-PIK3C3 complex. In addition, SRSF1 also directly interacts with PIK3C3 to disrupt the interaction between Beclin1 and PIK3C3. Consequently, the decrease of SRSF1 stabilizes the Beclin1 and PIK3C3 complex and activates autophagy. Interestingly, SRSF1 can be degraded by starvation- and oxidative stresses-induced autophagy through interacting with LC3-II, whereas reduced SRSF1 further promotes autophagy. This positive feedback is critical to inhibiting Gefitinib-resistant cancer cell progression both in vitro and in vivo. Consistently, the expression level of SRSF1 is inversely correlated to LC3 level in clinical cancer samples. Our study not only provides mechanistic insights of alternative splicing in autophagy regulation but also discovers a new regulatory role of SRSF1 in tumorigenesis, thereby offering a novel avenue for potential cancer therapeutics.
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