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MiR-4458-loaded gelatin nanospheres target COL11A1 for DDR2/SRC signaling pathway inactivation to suppress the progression of estrogen receptor-positive breast cancer.
- Source :
-
Biomaterials science [Biomater Sci] 2022 Aug 09; Vol. 10 (16), pp. 4596-4611. Date of Electronic Publication: 2022 Aug 09. - Publication Year :
- 2022
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Abstract
- RNA interference is a promising way to treat cancer and the construction of a stable drug delivery system is critically important for its application. Gelatin nanospheres (GNs) comprise a biodegradable drug vehicle with excellent biocompatibility, but there are limited studies on its delivery and role in the stabilization of miRNA and siRNA. Breast cancer is the most diagnosed type of female cancer worldwide. Abnormal miRNA expression is closely related to the occurrence and progression of estrogen receptor-positive (ER+) breast cancer. In this study, miR-4458 was upregulated in ER+ breast cancer and could inhibit MCF-7 cell viability, colony formation, migration, and invasion. Collagen type XI alpha 1 (COL11A1) was identified as a directly interacting protein of miR-4458 and an important component of the extracellular matrix. High COL11A1 expression was positively correlated with poor prognosis, lower overall survival, disease-free survival, and a late tumor-node-metastasis stage. COL11A1 knockdown could inhibit MCF-7 cell migration and invasion. GNs were used to load a miR-4458 mimic or COL11A1 siRNA (si-COL11A1) to achieve sustained and controlled release in xenograft nude mice. Their tumor volume was decreased, tumor cell apoptosis was promoted, and hepatic metastasis was significantly inhibited. Moreover, the DDR2/SRC signaling pathway was inactivated after transfection with the miR-4458 mimic and si-COL11A1. In conclusion, GNs can be potentially used to deliver siRNA or miRNA, and miR-4458 and COL11A1 can be possible targets for ER+ breast cancer treatment.
- Subjects :
- Animals
Cell Line, Tumor
Cell Proliferation
Collagen Type XI genetics
Collagen Type XI metabolism
Female
Gelatin metabolism
Gene Expression Regulation, Neoplastic
Humans
Mice
Mice, Nude
RNA, Small Interfering therapeutic use
Receptors, Estrogen genetics
Receptors, Estrogen metabolism
Receptors, Estrogen therapeutic use
Signal Transduction
src-Family Kinases
Breast Neoplasms drug therapy
Breast Neoplasms genetics
Breast Neoplasms pathology
Discoidin Domain Receptor 2 genetics
Discoidin Domain Receptor 2 metabolism
MicroRNAs metabolism
Nanospheres
Subjects
Details
- Language :
- English
- ISSN :
- 2047-4849
- Volume :
- 10
- Issue :
- 16
- Database :
- MEDLINE
- Journal :
- Biomaterials science
- Publication Type :
- Academic Journal
- Accession number :
- 35792605
- Full Text :
- https://doi.org/10.1039/d2bm00543c