ArticleMolecular cancer2022
The circROBO1/KLF5/FUS feedback loop regulates the liver metastasis of breast cancer by inhibiting the selective autophagy of afadin.
Article in Molecular cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 92 papers.
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92 citing papers in PubMed, 177 citations in OpenAlex.
- Stemness-Associated Biomarkers in Breast Cancer Liver Metastasis: Hepatic Adaptation, Prognostic Relevance, and Monitoring.Diagnostics (Basel, Switzerland) · 2026Review
- Cancer stem cell plasticity in shaping drug resistance landscapes in prostate cancer.Journal of advanced research · 2026Review
- Impact of Underlying Liver Disease on the Risk and Prognostic Factors of Breast Cancer Liver Metastases: A Retrospective Multicenter Cohort Study.Cancer medicine · 2026Article
- S6K1 overexpression enhances autophagy in breast cancer cells by inducing the translation of CLU.Chinese medical journal · 2026Article
- Stattic engineering M2 macrophage-derived exosomes mediate autophagy and immune reprogramming for secondary hyperparathyroidism.Journal of advanced research · 2026Article
- Circular RNAs in tumor immunity and immunotherapy of breast cancer.Frontiers in immunology · 2026Review
- The Role of Actin-Binding Proteins in Breast Cancer Progression.Breast cancer (Dove Medical Press) · 2026Review
- Splicing factor FUS facilitates the progression of PIT1-lineage PitNETs by upregulating MDM2.Theranostics · 2026Article
- Programmed cell death mechanisms of traditional plant medicine in prostate cancer therapy.Frontiers in immunology · 2026Review
- CircZFAND6 suppresses gastric cancer metastasis and reduces resistance to TKI therapy.Molecular cancer · 2025Article
- Review
- Knockdown of HGH1 in breast cancer cell lines can inhibit the viability, invasion and migration of tumor cells.Cell adhesion & migration · 2025Article
- The dual impact of oxidative stress on breast cancer.Scientific reports · 2025Article
- CircHPCAL1 promotes the progression of pancreatic cancer via the regulation of STEAP2.Clinical and translational medicine · 2025Article
- A novel feedback loop: CELF1/circ-CELF1/BRPF3/KAT7 in cardiac fibrosis.Acta pharmaceutica Sinica. B · 2025Article
- M6A-Methylated circRAPGEF5 drives lung adenocarcinoma progression and metastasis via IGF2BP2/NUP160-mediated autophagy suppression.Molecular cancer · 2025Article
- Expanded insights into the mechanisms of RNA-binding protein regulation of circRNA generation and function in cancer biology and therapy.Genes & diseases · 2025Review
- FUS Selectively Facilitates circRNAs Packing into Small Extracellular Vesicles within Hypoxia Neuron.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The circ_0054633/miR-590-3p/RUNX2 positive feedback loop promotes the osteogenic differentiation of BMSCs.Stem cell research & therapy · 2025Article
- The EGR1-mediated lncRNA TENM3-AS1 potentiates gastric cancer metastasis via reprogramming fatty acid metabolism.Molecular cancer · 2025Article
32 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMetastasis causes the majority of cancer-related deaths worldwide. Increasing studies have revealed that circRNAs are associated with the carcinogenesis and metastasis of many cancers. Nevertheless, the biological mechanisms of circRNAs in breast cancer (BC) liver metastasis remain extremely ambiguous.
methodsIn this study, we identified circROBO1 from three pairs of primary BC and metastatic liver sites by RNA sequencing. FISH assays and RT-qPCR were conducted to validate the existence and expression of circROBO1. The oncogenic role of circROBO1 was demonstrated both in vitro and in vivo. Western blot, ChIP, RIP, RNA pull-down, and dual-luciferase reporter assays were used to confirm the interaction of the feedback loop among circROBO1, miR-217-5p, KLF5, and FUS. Meanwhile, the regulation of selective autophagy was investigated by immunofluorescence, CoIP, and western blot.
resultsIn this study, upregulated expression of circROBO1 was found in BC-derived liver metastases and was correlated with poor prognosis. Knockdown of circROBO1 strikingly inhibited the proliferation, migration, and invasion of BC cells, whereas overexpression of circROBO1 showed the opposite effects. Moreover, overexpression of circROBO1 promoted tumor growth and liver metastasis in vivo. Further research revealed that circROBO1 could upregulate KLF5 by sponging miR-217-5p, allowing KLF5 to activate the transcription of FUS, which would promote the back splicing of circROBO1. Therefore, a positive feedback loop comprising circROBO1/KLF5/FUS was formed. More importantly, we found that circROBO1 inhibited selective autophagy of afadin by upregulating KLF5.
conclusionsOur results demonstrated that circROBO1 facilitates the carcinogenesis and liver metastasis of BC through the circROBO1/KLF5/FUS feedback loop, which inhibits the selective autophagy of afadin by suppressing the transcription of BECN1. Therefore, circROBO1 could be used not only as a potential prognostic marker but also as a therapeutic target in BC.
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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.