ArticleCancer research2015
Targeting of Runx2 by miR-135 and miR-203 Impairs Progression of Breast Cancer and Metastatic Bone Disease.
Article in Cancer research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 109 papers.
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Who cites it
109 citing papers in PubMed, 181 citations in OpenAlex.
- Trial
- Article
- Hijacking the bone niche: mechanistic insights into bone metastasis in breast cancer.Bone research · 2026Review
- Review
- miR-34c-5p targets Notch2 to promote fracture healing.Journal of orthopaedic surgery and research · 2025Article
- Unveiling Matrix Metalloproteinase 13's Dynamic Role in Breast Cancer: A Link to Physical Changes and Prognostic Modulation.International journal of molecular sciences · 2025Review
- Dual-regulatory miRNAs: master regulators and therapeutic targets in bone-metastatic breast cancer.Frontiers in molecular biosciences · 2025Review
- Reflections and perspectives on epigenetically mediated biological control: compromises in cancer and skeletal pathology.Academia biology · 2025Article
- MicroRNAs in bone metastases: mechanisms and research progression.Frontiers in oncology · 2025Review
- Molecular Signaling Pathways and MicroRNAs in Bone Remodeling: A Narrative Review.Diseases (Basel, Switzerland) · 2024Review
- The Involvement of microRNAs in Bone Remodeling Signaling Pathways and Their Role in the Development of Osteoporosis.Biology · 2024Review
- Role of RUNX2 in breast cancer development and drug resistance (Review).Oncology letters · 2023Review
- Bone serves as a transfer station for secondary dissemination of breast cancer.Bone research · 2023Review
- Review
- Inhibition of miR338 rescues cleidocranial dysplasia in Runx2 mutant mice partially via the Hif1a-Vegfa axis.Experimental & molecular medicine · 2023Article
- The Intricate Interplay between the ZNF217 Oncogene and Epigenetic Processes Shapes Tumor Progression.Cancers · 2022Review
- Review
- MiR-556-5p modulates migration, invasion, and epithelial-mesenchymal transition in breast cancer cells via targeting PTHrP.Journal of molecular histology · 2022Article
- Article
- Review
49 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
Abstract
Progression of breast cancer to metastatic bone disease is linked to deregulated expression of the transcription factor Runx2. Therefore, our goal was to evaluate the potential for clinical use of Runx2-targeting miRNAs to reduce tumor growth and bone metastatic burden. Expression analysis of a panel of miRNAs regulating Runx2 revealed a reciprocal relationship between the abundance of Runx2 protein and two miRNAs, miR-135 and miR-203. These miRNAs are highly expressed in normal breast epithelial cells where Runx2 is not detected, and absent in metastatic breast cancer cells and tissue biopsies that express Runx2. Reconstituting metastatic MDA-MB-231-luc cells with miR-135 and miR-203 reduced the abundance of Runx2 and expression of the metastasis-promoting Runx2 target genes IL11, MMP-13, and PTHrP. In addition, tumor cell viability was decreased and migration suppressed in vitro. Orthotopic implantation of MDA-MB-231-luc cells delivered with miR-135 or miR-203, followed by an intratumoral administration of the synthetic miRNAs, reduced the tumor growth and spontaneous metastasis to bone. Furthermore, intratibial injection of these miRNA-delivered cells impaired tumor growth in the bone environment and inhibited bone resorption. Importantly, reconstitution of Runx2 in MDA-MB-231-luc cells delivered with miR-135 and miR-203 reversed the inhibitory effect of the miRNAs on tumor growth and metastasis. Thus, we have identified that aberrant expression of Runx2 in aggressive tumor cells is related to the loss of specific Runx2-targeting miRNAs and that a clinically relevant replacement strategy by delivery of synthetic miRNAs is a candidate for a therapeutic approach to prevent metastatic bone disease by this route.
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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.