| Title: |
Protective effects of miR-24-2-5p in early stages of breast cancer bone metastasis |
| Authors: |
Puppo, M.; Croset, M.; Ceresa, D.; Valluru, M.K.; Canuas Landero, V.G.; Hernandez Guadarrama, M.; Iuliani, M.; Pantano, F.; Dawn Ottewell, P.; Clézardin, P. |
| Publisher Information: |
Springer Science and Business Media LLC |
| Publication Year: |
2024 |
| Collection: |
White Rose Research Online (Universities of Leeds, Sheffield & York) |
| Description: |
Background Bone is the most frequent site of metastasis for breast cancer (BC). Metastatic BC cells interact with bone cells, including osteoclasts and osteoblasts, creating a cancer niche where they seed and proliferate. MicroRNAs (miRNAs) are regulators of breast-to-bone metastasis progression. MiR-24-2-5p has previously been shown to have roles in both breast cancer progression and inhibition of osteogenic differentiation. However, a direct link between miR-24-2-5p activity and the onset of bone metastasis remains ill-defined. Methods Analysis of the expression of miR-24 forms (miR-24-2-5p, miR-24-3p, miR-24-1-5p) in the serum from early-stage BC patients at baseline (time of surgery) was conducted. MiR-24-2-5p overexpression in BC cells (NW1, a luc2-positive subpopulation of MDA-MB-231, and MCF7) was obtained by miRNA mimic transfection or lentivirus transduction. MiR-24-2-5p downregulation in BC cells (ZR-75-1, T-47D, SK-BR-3) was obtained by miRNA inhibitor transfection. Cell proliferation, migration and/or invasion assays were performed to assess BC cell functions after modulation of miR-24-2-5p expression. An animal model was used to assess the effect of miR-24-2-5p overexpression on early BC metastasis formation, as judged by bioluminescence imaging, and on bone remodelling, following measurement of circulating bone resorption (CTX-I) and bone formation (P1NP) markers. The effect of conditioned medium from miR-24-2-5p-overexpressing BC cells on human and murine osteoclast differentiation was investigated. Endogenous miR-24-2-5p expression levels were also quantified during murine osteoclast differentiation. RNA-sequencing (RNA-seq) analysis of BC cells was performed to evaluate transcriptomic changes associated with miR-24-2-5p overexpression. Selected modulated transcripts upon miR-24-2-5p overexpression were further validated by real-time qPCR. Results Low expression levels of miR-24-2-5p, but not other miR-24 forms (miR-24-3p, miR-24-1-5p), in the serum from early-stage BC patients were associated ... |
| Document Type: |
article in journal/newspaper |
| File Description: |
text |
| Language: |
English |
| ISSN: |
1465-5411 |
| Relation: |
https://eprints.whiterose.ac.uk/id/eprint/221245/1/s13058-024-01934-2.pdf; Puppo, M., Croset, M., Ceresa, D. et al. (7 more authors) (2024) Protective effects of miR-24-2-5p in early stages of breast cancer bone metastasis. Breast Cancer Research, 26. 186. ISSN: 1465-5411 |
| DOI: |
10.1186/s13058-024-01934-2 |
| Availability: |
https://eprints.whiterose.ac.uk/id/eprint/221245/; https://doi.org/10.1186/s13058-024-01934-2 |
| Rights: |
cc_by_4 |
| Accession Number: |
edsbas.770831A2 |
| Database: |
BASE |