ArticleClinical and translational medicine2025
RNF31 induces paclitaxel resistance by sustaining ALYREF cytoplasmic-nuclear shuttling in human triple-negative breast cancer.
Article in Clinical and translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.
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Who cites it
11 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Pooled it
- The NEK8/ALYREF axis promotes cisplatin resistance in bladder cancer by stabilizing CDK18 mRNA to facilitate DNA damage repair.Cell death and differentiation · 2026Article
- Extracellular signal-regulated kinase 3 forms a nuclear complex with Aly/REF export factor and the splicing factor proline and glutamine rich to exacerbate pathological cardiac remodeling due to pressure overload.Molecular biomedicine · 2026Article
- CASC19 stabilization by ALYREF via m5C modification and its impact on SCD in colorectal cancer cell aggressiveness and stemness.Cell & bioscience · 2026Article
- Solasonine inhibits NSCLC malignant progression by regulating SLC7A11 ubiquitination degradation and inducing ferroptosis.Respiratory research · 2026Article
- OTUB2/ALYREF axis modulates the docetaxel resistance of castration-resistant prostate cancer via upregulating ABCG4-mediated drug efflux.International journal of biological sciences · 2026Article
- RNA m5C methylation in cancer: mechanisms and biological impact.Oncogenesis · 2025Review
- Rewriting the Fate of Cancer: Epigenetic and Epitranscriptomic Regulators in the Metastatic Cascade.Biomolecules · 2025Review
- TUBB3 (βIII-tubulin) drives gastric cancer progression and poor prognosis by regulating cell cycle and invadopodia formation.Cancer biomarkers : section A of Disease markers · 2025Article
- RNF31 induces paclitaxel resistance by sustaining ALYREF cytoplasmic-nuclear shuttling in human triple-negative breast cancer.Clinical and translational medicine · 2025Article
- Exploring the impact of cuproptosis on prostate cancer prognosisFrontiers in pharmacology · 2025Article
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18 authors.
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Abstract
backgroundResistance to paclitaxel-based chemotherapy is the major obstacle in triple-negative breast cancer (TNBC) treatment. However, overcoming paclitaxel resistance remains an unsolved problem. The present study aimed to determine whether paclitaxel treatment impairs Aly/REF export factor (ALYREF) cytoplasmic-nuclear shuttling, its mechanism, and the role of ubiquitinated ALYREF in paclitaxel resistance.
methodsThe subcellular proportion of ALYREF was detected in samples from patients with TNBC using immunohistochemistry to analyze the relationship between ALYREF distribution and paclitaxel response. Cell viability assays, immunofluorescence assays, quantitative real-time reverse transcription PCR assays, western blotting, and terminal deoxynucleotidyl transferase nick-end-labelling assays were conducted to measure the biological function of the subcellular proportion of ALYREF and E3 ligase ring finger protein 31 (RNF31) on paclitaxel sensitivity in TNBC. The synergistic effects of an RNF31 inhibitor plus paclitaxel on TNBC were evaluated. Cox regression models were adopted to assess the prognostic role of RNF31 in TNBC.
resultsHerein, we showed that regulation of ALYREF cytoplasmic-nuclear shuttling is associated with the paclitaxel response in TNBC. In paclitaxel-sensitive TNBC, ALYREF was trapped in the cytoplasm by paclitaxel, while in paclitaxel-resistant TNBC, ALYREF was efficiently transported into the nucleus to exert its function, allowing the export of the mRNAs encoding paclitaxel-resistance-related factors, including tubulin beta 3 class III (TUBB3), stathmin 1 (STMN1), and microtubule-associated protein Tau (TAU), ultimately inducing paclitaxel resistance in TNBC. Mechanistically, we found that RNF31 interacts with and ubiquitinates ALYREF, which facilitates ALYREF nuclear transportation via importin 13 (IPO13) under paclitaxel treatment. Notably, the RNF31 inhibitor and paclitaxel synergistically repressed tumour growth in vivo and in TNBC patient-derived organoids. In addition, analysis of patients with TNBC showed that elevated RNF31 levels correlated with poor prognosis.
conclusionThese data indicated that RNF31-mediated ALYREF ubiquitylation could represent a potent target to reverse paclitaxel resistance in TNBC. KEY POINTS: RNF31 facilitated ALYREF-mediated PTX resistance in TNBC. RNF31 promoted ALYREF nuclear transport via IPO13 in response to PTX treatment, subsequently enhancing the export of mRNAs encoding PTX resistance-related factors, including TUBB3, STMN1, and TAU. Blocking RNF31 trapped ALYREF in the cytoplasm and induced TNBC cell death upon PTX treatment. Inhibiting RNF31 activity re-sensitized PTX-resistant TNBC to PTX treatment.
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