ArticleMolecular therapy : the journal of the American Society of Gene Therapy2020
Timeless-Stimulated miR-5188-FOXO1/β-Catenin-c-Jun Feedback Loop Promotes Stemness via Ubiquitination of β-Catenin in Breast Cancer.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 1 of them a synthesis that pooled it.
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Who cites it
51 citing papers in PubMed, 1 synthesis or guideline pooled it, 79 citations in OpenAlex.
- Night-shift work, breast cancer incidence, and all-cause mortality: an updated meta-analysis of prospective cohort studies.Sleep & breathing = Schlaf & Atmung · 2022Pooled it
- TIMELESS promotes glioma stemness and malignancy through JAK-STAT3 pathway.The Journal of biological chemistry · 2026Article
- Three-dimensional spheroid models in breast cancer: tumor microenvironment complexity, cancer stem cell-driven resistance, and translational model integration.Journal of translational medicine · 2026Review
- miR-3648 regulates cell functions and acts as a potential biomarker to predict prognosis in breast cancer and its bioinformatics analysis.World journal of surgical oncology · 2026Article
- S100B induces angiogenesis via the clathrin/FOXO1/β-catenin signaling pathway and contributes to Bevacizumab resistance in epithelial ovarian cancer.Journal of advanced research · 2026Article
- TIMELESS Promotes LUAD Growth via Suppressing Transferrin-Mediated Ferroptosis and Reprograms the Tumor Microenvironment against Anti-PD-1 Immunotherapy.Cancer communications (London, England) · 2026Article
- Dual-targeted N-PMIMaterials today. Bio · 2025Article
- Effect of miR-6767-5p on breast cancer cell phenotype and its regulatory mechanism.Scientific reports · 2025Article
- Identification and validation of genes related to stem cells and telomere maintenance mechanisms as biomarkers for breast cancer.Frontiers in immunology · 2025Article
- KCTD10 inhibits lung cancer metastasis and angiogenesis via ubiquitin-mediated β-catenin degradation.Frontiers in immunology · 2025Article
- Circadian genes and non-coding RNAs: interactions and implications in cancer.Animal cells and systems · 2025Review
- Tumor-secreted LCN2 impairs gastric cancer progression via autocrine inhibition of the 24p3R/JNK/c-Jun/SPARC axis.Cell death & disease · 2024Article
- IncreasedThe Journal of international medical research · 2024Article
- Epigenetics and environmental health.Frontiers of medicine · 2024Review
- CD146, a therapeutic target involved in cell plasticity.Science China. Life sciences · 2024Review
- Nicotine-induced activation of cholinergic receptor nicotinic alpha 5 subunit mediates the malignant behaviours of laryngeal squamous epithelial cells by interacting with RABL6.Cell death discovery · 2024Article
- Enhanced anticancer synergy of LOM612 in combination with selinexor: FOXO1 nuclear translocation-mediated inhibition of Wnt/β-catenin signaling pathway in breast cancer.Cancer chemotherapy and pharmacology · 2024Article
- Article
- SP3-induced Timeless transcription contributes to cell growth of lung adenocarcinoma cells.PloS one · 2024Article
- β-catenin inhibitors in cancer therapeutics: intricacies and way forward.Bioengineered · 2023Review
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
MicroRNAs (miRNAs) play an essential role in the self-renewal of breast cancer stem cells (BCCs). Our study aimed to clarify the role of proto-oncogene c-Jun-regulated miR-5188 in breast cancer progression and its association with Timeless-mediated cancer stemness. In the present study, we showed that miR-5188 exerted an oncogenic effect by inducing breast cancer stemness, proliferation, metastasis, and chemoresistance in vitro and in vivo. The mechanistic analysis demonstrated that miR-5188 directly targeted FOXO1, which interacted with β-catenin in the cytoplasm, facilitated β-catenin degradation, and impaired the nuclear accumulation of β-catenin, thus stimulating the activation of known Wnt targets, epithelial-mesenchymal transition (EMT) markers, and key regulators of cancer stemness. Moreover, miR-5188 potentiated Wnt/β-catenin/c-Jun signaling to promote breast cancer progression. Interestingly, c-Jun enhanced miR-5188 transcription to form a positive regulatory loop, and Timeless interacted with Sp1/c-Jun to induce miR-5188 expression by promoting c-Jun-mediated transcription, which further activated miR-5188-FOXO1/β-catenin-c-Jun loop and facilitated breast cancer progression. Importantly, miR-5188 was upregulated in breast cancer and was positively correlated with poor patient prognosis. This study identifies miR-5188 as a novel oncomiR and provides a new theoretical basis for the clinical use of miR-5188 antagonists in the treatment of breast cancer.
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