| Title: |
MiR-662 is associated with metastatic relapse in early-stage breast cancer and promotes metastasis by stimulating cancer cell stemness |
| Authors: |
Puppo, M.; Valluru, M.K.; Croset, M.; Ceresa, D.; Iuliani, M.; Khan, A.; Wicinski, J.; Charafe-Jauffret, E.; Ginestier, C.; Pantano, F.; Ottewell, P.D.; Clézardin, P. |
| Publisher Information: |
Springer Science and Business Media LLC |
| Publication Year: |
2023 |
| Collection: |
White Rose Research Online (Universities of Leeds, Sheffield & York) |
| Description: |
Background Breast cancer (BC) metastasis, which often occurs in bone, contributes substantially to mortality. MicroRNAs play a fundamental role in BC metastasis, although microRNA-regulated mechanisms driving metastasis progression remain poorly understood. Methods MiRome analysis in serum from BC patients was performed by TaqMan™ low-density array. MiR-662 was overexpressed following MIMIC-transfection or lentivirus transduction. Animal models were used to investigate the role of miR-662 in BC (bone) metastasis. The effect of miR-662-overexpressing BC cell conditioned medium on osteoclastogenesis was investigated. ALDEFLUOR assays were performed to study BC stemness. RNA-sequencing transcriptomic analysis of miR-662-overexpressing BC cells was performed to evaluate gene expression changes. Results High levels of hsa-miR-662 (miR-662) in serum from BC patients, at baseline (time of surgery), were associated with future recurrence in bone. At an early-stage of the metastatic disease, miR-662 could mask the presence of BC metastases in bone by inhibiting the differentiation of bone-resorbing osteoclasts. Nonetheless, metastatic miR-662-overexpressing BC cells then progressed as overt osteolytic metastases thanks to increased stem cell-like traits. Conclusions MiR-662 is involved in BC metastasis progression, suggesting it may be used as a prognostic marker to identify BC patients at high risk of metastasis. |
| Document Type: |
article in journal/newspaper |
| File Description: |
text |
| Language: |
English |
| ISSN: |
0007-0920 |
| Relation: |
https://eprints.whiterose.ac.uk/id/eprint/202953/1/s41416-023-02340-9.pdf; Puppo, M. orcid.org/0000-0003-1409-9577 , Valluru, M.K. orcid.org/0000-0001-9156-866X , Croset, M. et al. (9 more authors) (2023) MiR-662 is associated with metastatic relapse in early-stage breast cancer and promotes metastasis by stimulating cancer cell stemness. British Journal of Cancer, 129 (5). pp. 754-771. ISSN: 0007-0920 |
| Availability: |
https://eprints.whiterose.ac.uk/id/eprint/202953/ |
| Rights: |
cc_by_4 |
| Accession Number: |
edsbas.E350B6B9 |
| Database: |
BASE |