ArticleOncogene2023
The sodium channel subunit SCNN1B suppresses colorectal cancer via suppression of active c-Raf and MAPK signaling cascade.
Article in Oncogene, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 18 citations in OpenAlex.
- Integrated bioinformatics and experimental validation identify FOXQ1, GRIN2D, and SCNN1B as novel biomarkers for distinguishing high-risk sessile serrated lesions from hyperplastic polyps.Journal of molecular histology · 2026Article
- ALOXE3 expression predicts poor prognosis and modulates immune infiltration in colon adenocarcinoma.World journal of surgical oncology · 2025Article
- Bayesian inference of genetic pleiotropy identifies drug targets and repurposable medicines for human complex diseases.medRxiv : the preprint server for health sciences · 2025Article
- Prediction of neuroblastoma prognosis with a novel T-cell exhaustion-related gene signature.Scientific reports · 2025Article
- Multimodal analysis of TAAD pathogenesis: SHAP-enhanced interpretable models and single-cell sequencing analysis reveal immune microenvironment alterations.Frontiers in immunology · 2025Article
- Review
- Targeting KAT7 inhibits the progression of colorectal cancer.Theranostics · 2025Article
- Integrated machine learning analysis of 30 cell death patterns identifies a novel prognostic signature in glioma.Frontiers in cell and developmental biology · 2025Article
- N-carbamylglutamate supplementation improves laying performance of layers by regulating hypothalamic-pituitary-ovarian axis.Frontiers in veterinary science · 2025Article
- 5-Hydroxymethylcytosine Profiles of cfDNA in Urine as Diagnostic, Differential Diagnosis and Prognostic Markers for Multiple Myeloma.Cancer medicine · 2024Article
- Joint Screening for Ultra-High Dimensional Multi-Omics Data.Bioengineering (Basel, Switzerland) · 2024Article
- Molecular subtyping and the construction of a predictive model of colorectal cancer based on ion channel genes.European journal of medical research · 2024Article
- Genes associated with inflammation for prognosis prediction for clear cell renal cell carcinoma: a multi-database analysis.Translational cancer research · 2023Article
- Identification of heterogeneous subtypes and a prognostic model for gliomas based on mitochondrial dysfunction and oxidative stress-related genes.Frontiers in immunology · 2023Article
- SVM-DO: identification of tumor-discriminating mRNA signatures via support vector machines supported by Disease Ontology.Turkish journal of biology = Turk biyoloji dergisi · 2023Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The incidence of colorectal cancer (CRC) is rising worldwide. Here, we identified SCNN1B as an outlier down-regulated in CRC and it functions as a tumor suppressor. SCNN1B mRNA and protein expression were down-regulated in primary CRC and CRC cells. In a tissue microarray cohort (N = 153), SCNN1B protein was an independent prognostic factor for favorable outcomes in CRC. Ectopic expression of SCNN1B in CRC cell lines suppressed cell proliferation, induced apoptosis, and cell cycle arrest, and suppressed cell migration in vitro. Xenograft models validated tumor suppressive function of SCNN1B in vivo. Mechanistically, Gene Set Enrichment Analysis (GSEA) showed that SCNN1B correlates with KRAS signaling. Consistently, MAPK qPCR and kinase arrays revealed that SCNN1B suppressed MAPK signaling. In particular, SCNN1B overexpression suppressed p-MEK/p-ERK expression and SRE-mediated transcription activities, confirming blockade of Ras-Raf-MEK-ERK cascade. Mechanistically, SCNN1B did not affect KRAS activation, instead impairing activation of c-Raf by inducing its inhibitory phosphorylation and targeting active c-Raf for degradation. The ectopic expression of c-Raf fully rescued cell proliferation and colony formation in SCNN1B-overexpressing CRC cells, confirming c-Raf as the principal molecular target of SCNN1B. In summary, we identified SCNN1B as a tumor suppressor by functioning as a c-Raf antagonist, which in turn suppressed oncogenic MEK-ERK signaling.
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