ArticleMolecular cancer2021
Circular RNA circIKBKB promotes breast cancer bone metastasis through sustaining NF-κB/bone remodeling factors signaling.
Article in Molecular cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 118 citations in OpenAlex.
- Breaking the immune "cold niche" in bone metastasis: core mechanisms of the multidimensional interwoven regulatory network and precision breakthrough strategies.Molecular cancer · 2026Review
- Decoding triple negative breast cancer bone metastasis: from 3D bioprinted models to clinical translation.Journal of nanobiotechnology · 2026Review
- Hijacking the bone niche: mechanistic insights into bone metastasis in breast cancer.Bone research · 2026Review
- Mechanisms of breast cancer dormancy in bone metastasis.Clinical & experimental metastasis · 2026Review
- Small interfering RNA (siRNA)-based targeting breast cancer therapy.Discover oncology · 2026Review
- EIF4A3-induced circUBAC2 promotes lung cancer progression via regulation of the Hippo signaling pathway.Cellular & molecular biology letters · 2026Article
- The crosstalk network of non-coding RNAs: Emerging opportunities for the clinical application of osteoporosis.Non-coding RNA research · 2026Review
- Identification and validation of biomarkers of Shenggu Zaizao Wan in the treatment of steroid-induced osteonecrosis of the femoral head by integrating network pharmacology and bulk transcriptomic.Frontiers in medicine · 2026Article
- Astragalin Attenuates Bone Destruction and the Progression of Bone Metastasis in Breast Cancer.Cancers · 2025Article
- Defining the Tumor-Bone axis: the role of extracellular vesicles in a crucial exchange route for breast cancer development and progression.Clinical & experimental metastasis · 2025Review
- Circular RNAs orchestrating breast cancer hallmarks: bridging tumor biology and therapy resistance.Functional & integrative genomics · 2025Review
- Decoding the functional roles of circular RNAs linked to NF-κB pathway in carcinogenesis.Discover oncology · 2025Review
- Regulatory roles of circular RNAs in Wnt and other oncogenic signaling pathways in breast cancer progression: a comprehensive review.European journal of medical research · 2025Review
- Epigenetic Modulation and Bone Metastasis: Evolving Therapeutic Strategies.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Role of ncRNAs in the Development of Chronic Pain.Non-coding RNA · 2025Review
- EIF4A3-Induced circ_0029941 Promotes Astrocyte Activation Through Enhancing Autophagy via miR-224-5p/NFAT5 Axis.Molecular neurobiology · 2025Article
- Targeting inflammation in cancer therapy: from mechanistic insights to emerging therapeutic approaches.Journal of translational medicine · 2025Review
- Estrogen receptor β inhibits breast cancer migration and promotes its apoptosis through NF-κB/IL-8 signaling.Translational cancer research · 2025Article
- Article
- RNA-Binding Proteins (RBPs) and Circular RNA Biogenesis.Advances in experimental medicine and biology · 2025Review
12 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundBreast cancer (BC) has a marked tendency to spread to the bone, resulting in significant skeletal complications and mortality. Recently, circular RNAs (circRNAs) have been reported to contribute to cancer initiation and progression. However, the function and mechanism of circRNAs in BC bone metastasis (BC-BM) remain largely unknown.
methodsBone-metastatic circRNAs were screened using circRNAs deep sequencing and validated using in situ hybridization in BC tissues with or without bone metastasis. The role of circIKBKB in inducing bone pre-metastatic niche formation and bone metastasis was determined using osteoclastogenesis, immunofluorescence and bone resorption pit assays. The mechanism underlying circIKBKB-mediated activation of NF-κB/bone remodeling factors signaling and EIF4A3-induced circIKBKB were investigated using RNA pull-down, luciferase reporter, chromatin isolation by RNA purification and enzyme-linked immunosorbent assays.
resultsWe identified that a novel circRNA, circIKBKB, was upregulated significantly in bone-metastatic BC tissues. Overexpressing circIKBKB enhanced the capability of BC cells to induce formation of bone pre-metastatic niche dramatically by promoting osteoclastogenesis in vivo and in vitro. Mechanically, circIKBKB activated NF-κB pathway via promoting IKKβ-mediated IκBα phosphorylation, inhibiting IκBα feedback loop and facilitating NF-κB to the promoters of multiple bone remodeling factors. Moreover, EIF4A3, acted acting as a pre-mRNA splicing factor, promoted cyclization of circIKBKB by directly binding to the circIKBKB flanking region. Importantly, treatment with inhibitor eIF4A3-IN-2 reduced circIKBKB expression and inhibited breast cancer bone metastasis effectively.
conclusionWe revealed a plausible mechanism for circIKBKB-mediated NF-κB hyperactivation in bone-metastatic BC, which might represent a potential strategy to treat breast cancer bone metastasis.
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