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Exosomal miR-500a-5p derived from cancer-associated fibroblasts promotes breast cancer cell proliferation and metastasis through targeting USP28.
- Source :
-
Theranostics [Theranostics] 2021 Feb 06; Vol. 11 (8), pp. 3932-3947. Date of Electronic Publication: 2021 Feb 06 (Print Publication: 2021). - Publication Year :
- 2021
-
Abstract
- The tumor microenvironment contributes to tumor progression and metastasis. Cancer-associated fibroblasts (CAFs) form a major cellular component of the tumor microenvironment. In this study, we further explored the mechanisms underlying the tumor-promoting roles of CAFs. Methods: Patient-derived CAFs and normal fibroblasts (NFs) were isolated from breast carcinomas and adjacent normal breast tissue. Exosomes were isolated by ultracentrifugation and CAF-derived exosomal microRNAs were screened using next-generation sequencing technology. MiR-500a-5p expression was assessed by quantitative real-time polymerase chain reaction (qRT-PCR) and in situ hybridization; Tumor cell proliferation was determined by MTT assays and three-dimensioned (3D) cultures, and tumor metastasis was determined by Transwell assays in vitro . In vivo assays were performed in a nude mouse subcutaneous xenograft model. Results: We confirmed that CAF-derived exosomes significantly promoted the proliferation and metastasis of breast cancer cells. MiR-500a-5p was highly expressed in MDA-MB-231 and MCF7 cells treated with CAF-derived exosomes. The upregulation of miR-500a-5p was also confirmed in CAFs and CAF-derived exosomes. MiR-500a-5p was transferred from CAFs to the cancer cells, and subsequently promoted proliferation and metastasis by binding to ubiquitin-specific peptidase 28 (USP28). Conclusions: The present study demonstrates that CAFs promote breast cancer progression and metastasis via exosomal miR-500a-5p and indicate that inhibiting CAF-derived miR-500a-5p is an alternative modality for the treatment of breast cancer.<br />Competing Interests: Competing Interests: The authors have declared that no competing interest exists.<br /> (© The author(s).)
- Subjects :
- Animals
Breast Neoplasms pathology
Cell Line, Tumor
Cell Movement genetics
Cell Proliferation genetics
Coculture Techniques
Exosomes genetics
Exosomes metabolism
Female
Heterografts
Humans
MCF-7 Cells
Mice
Mice, Inbred BALB C
Mice, Nude
MicroRNAs metabolism
Models, Biological
Neoplasm Metastasis genetics
Precision Medicine
Ubiquitin Thiolesterase genetics
Up-Regulation
Breast Neoplasms genetics
Breast Neoplasms metabolism
Cancer-Associated Fibroblasts metabolism
MicroRNAs genetics
Ubiquitin Thiolesterase metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1838-7640
- Volume :
- 11
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Theranostics
- Publication Type :
- Academic Journal
- Accession number :
- 33664871
- Full Text :
- https://doi.org/10.7150/thno.53412