ArticleCell reports2015
Downregulation of the Ubiquitin Ligase RNF125 Underlies Resistance of Melanoma Cells to BRAF Inhibitors via JAK1 Deregulation.
Article in Cell reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
What it found
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Who cites it
52 citing papers in PubMed, 75 citations in OpenAlex.
- Construction of a diagnostic model for tuberculosis based on long non-coding RNA.Annals of medicine · 2026Article
- RNF125 mediates the anti-breast cancer activity of betulinic acid through ubiquitin-dependent degradation of MYH9.International journal of clinical oncology · 2026Article
- Exploiting Ubiquitination: African Swine Fever Virus-Mediated Recruitment of Host E3 Ligases During Viral Infection and Immune Regulation.Pathogens (Basel, Switzerland) · 2026Review
- RNF125 promotes CD8 T cell-mediated anticancer immunity and suppresses the malignant phenotype of cervical cancer.Molecular and cellular biochemistry · 2026Article
- Article
- The enigma of the RING-UIM E3 ligases: its transformative impact on cancer research.Journal of translational medicine · 2025Review
- Article
- SOX10, MITF, and microRNAs: Decoding their interplay in regulating melanoma plasticity.International journal of cancer · 2025Review
- Molecular Basis of BRAF Inhibitor Resistance in Melanoma: A Systematic Review.Pharmaceuticals (Basel, Switzerland) · 2025Review
- RNA‑binding protein MBNL1 regulates tumor growth, chemosensitivity and antitumor immunity in lung adenocarcinoma by controlling the expression of tumor suppressor RNF125.Oncology reports · 2025Article
- Keratin 6A promotes skin inflammation through JAK1-STAT3 activation in keratinocytes.Journal of biomedical science · 2025Article
- Genetic alterations in thyroid cancer mediating both resistance to BRAF inhibition and anaplastic transformation.Oncotarget · 2024Article
- Article
- Hypermethylation of RNF125 promotes autophagy-induced oxidative stress in asthma by increasing HMGB1 stability.iScience · 2023Article
- RNF125 attenuates hepatocellular carcinoma progression by downregulating SRSF1-ERK pathway.Oncogene · 2023Article
- E3 Ubiquitin Ligase RNF125 Suppresses Immune Escape in Head and Neck Squamous Cell Carcinoma by Regulating PD-L1 Expression.Molecular biotechnology · 2023Article
- Activation of the JAK/STAT Pathway Leads to BRAF Inhibitor Resistance in BRAFV600E Positive Thyroid Carcinoma.Molecular cancer research : MCR · 2023Article
- EHBP1L1 Drives Immune Evasion in Renal Cell Carcinoma through Binding and Stabilizing JAK1.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- BRAF Inhibitor Resistance in Melanoma: Mechanisms and Alternative Therapeutic Strategies.Current treatment options in oncology · 2022Review
- DNA promoter hypermethylation of melanocyte lineage genes determines melanoma phenotype.JCI insight · 2022Article
Corrections and comments
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Authors and funding
19 authors at 9 institutions in 4 countries.
Funding
Abstract
Despite the remarkable clinical response of melanoma harboring BRAF mutations to BRAF inhibitors (BRAFi), most tumors become resistant. Here, we identified the downregulation of the ubiquitin ligase RNF125 in BRAFi-resistant melanomas and demonstrated its role in intrinsic and adaptive resistance to BRAFi in cultures as well as its association with resistance in tumor specimens. Sox10/MITF expression correlated with and contributed to RNF125 transcription. Reduced RNF125 was associated with elevated expression of receptor tyrosine kinases (RTKs), including EGFR. Notably, RNF125 altered RTK expression through JAK1, which we identified as an RNF125 substrate. RNF125 bound to and ubiquitinated JAK1, prompting its degradation and suppressing RTK expression. Inhibition of JAK1 and EGFR signaling overcame BRAFi resistance in melanoma with reduced RNF125 expression, as shown in culture and in in vivo xenografts. Our findings suggest that combination therapies targeting both JAK1 and EGFR could be effective against BRAFi-resistant tumors with de novo low RNF125 expression.
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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.