ArticleOncogene2023
NRF2 has a splicing regulatory function involving the survival of motor neuron (SMN) in non-small cell lung cancer.
Article in Oncogene, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 11 citations in OpenAlex.
- Pharmacological Activation of NRF2 by Omaveloxolone Upregulates NRF2-Target Proteins in SMA Type I Human Fibroblasts.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Multi-omics analysis identifies a major histocompatibility complex class II-associated antigen-presenting cancer-associated fibroblast-like state linked to the nuclear factor erythroid 2-related factor 2-karyopherin subunit beta 1 axis in nonsmall cell lung cancer.Journal of cell communication and signaling · 2026Article
- SRSF9 mediates oncogenic RNA splicing of SLC37A4 via liquid-liquid phase separation to promote oral cancer progression.Journal of advanced research · 2026Article
- Reproductive Toxicity and Transgenerational Effects of Anesthetic Etomidate in Zebrafish: PCOS-like Ovarian Changes, Oxidative Stress, and Metabolism Disruption.Environment & health (Washington, D.C.) · 2025Article
- Beyond Antioxidants: The Emerging Role of Nrf2 Activation in Amyotrophic Lateral Sclerosis (ALS).International journal of molecular sciences · 2025Review
- A Low Expression of NRF2 Enhances Oxidative Stress and Autophagy in Myofibroblasts, Promoting Progression of Chronic Obstructive Pulmonary Disease.Current medicinal chemistry · 2025Article
- Genetic Variability in Oxidative Stress, Inflammatory, and Neurodevelopmental Pathways: Impact on the Susceptibility and Course of Spinal Muscular Atrophy.Cellular and molecular neurobiology · 2024Article
- Physiological Features of the Neural Stem Cells Obtained from an Animal Model of Spinal Muscular Atrophy and Their Response to Antioxidant Curcumin.International journal of molecular sciences · 2024Article
- The Experimental and In Silico-Based Evaluation of NRF2 Modulators, Sulforaphane and Brusatol, on the Transcriptome of Immortalized Bovine Mammary Alveolar Cells.International journal of molecular sciences · 2024Article
- Metformin suppresses NFE2L1 pathway activation to inhibit gap junction beta protein expression in NSCLC.Cancer medicine · 2024Article
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The nuclear factor erythroid 2-like 2 (NFE2L2; NRF2) signaling pathway is frequently deregulated in human cancers. The critical functions of NRF2, other than its transcriptional activation, in cancers remain largely unknown. Here, we uncovered a previously unrecognized role of NRF2 in the regulation of RNA splicing. Global splicing analysis revealed that NRF2 knockdown in non-small cell lung cancer (NSCLC) A549 cells altered 839 alternative splicing (AS) events in 485 genes. Mechanistic studies demonstrated that NRF2 transcriptionally regulated SMN mRNA expression by binding to two antioxidant response elements in the SMN1 promoter. Post-transcriptionally, NRF2 was physically associated with the SMN protein. The Neh2 domain of NRF2, as well as the YG box and the region encoded by exon 7 of SMN, were required for their interaction. NRF2 formed a complex with SMN and Gemin2 in nuclear gems and Cajal bodies. Furthermore, the NRF2-SMN interaction regulated RNA splicing by expressing SMN in NRF2-knockout HeLa cells, reverting some of the altered RNA splicing. Moreover, SMN overexpression was significantly associated with alterations in the NRF2 pathway in patients with lung squamous cell carcinoma from The Cancer Genome Atlas. Taken together, our findings suggest a novel therapeutic strategy for cancers involving an aberrant NRF2 pathway.
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