Back to Search
Start Over
Mir‐34a and mir‐200c have an additive tumor‐suppressive effect on breast cancer cells and patient prognosis
- Source :
- Mansoori, B, Silvestris, N, Mohammadi, A, Khaze, V, Baghbani, E, Mokhtarzadeh, A, Shanehbandi, D, Derakhshani, A, Duijf, P H G & Baradaran, B 2021, ' Mir-34a and mir-200c have an additive tumor-suppressive effect on breast cancer cells and patient prognosis ', Genes, vol. 12, no. 2, 267 . https://doi.org/10.3390/genes12020267, Genes, Vol 12, Iss 267, p 267 (2021), Genes, Volume 12, Issue 2
- Publication Year :
- 2021
-
Abstract
- Breast cancer is the most common women’s malignancy in the world and, for subgroups ofpatients, treatment outcomes remain poor. Thus, more effective therapeutic strategies are urgently needed. MicroRNAs (miRNAs) have emerged as promising therapeutic tools and targets, as they play significant roles in regulating key cellular processes by suppressing gene expression. However, additive opportunities involving miRNAs have been underexplored. For example, both miR-34aand miR-200c individually suppress the development of different types of cancer, but the cellular effects of their combined actions remain unknown. Here, we show that miR-34a and miR-200c levels are reduced in breast tumors compared to adjacent normal tissues and that this additively predicts poor patient survival. In addition, in cell lines, miR-34a and miR-200c additively induce apoptosis and cell cycle arrest, while also inhibiting proliferation, invasion, migration, stemness andepithelial-to-mesenchymal transition (EMT). Mechanistically, both miRNA-34a and miR-200c directly target HIF1-α and subsequently downregulate VEGFR, MMP9 and CXCR4, although combined miRNA-34a and miR-200c delivery suppresses mouse xenograft tumor development as effectively as individual delivery. We establish a model, supported by in vitro and clinical data, which collectively suggest that the co-delivery of miR-34a and miR-200c represents a promising novel therapeuticstrategy for breast cancer patients. Breast cancer is the most common women’s malignancy in the world and, for subgroups of patients, treatment outcomes remain poor. Thus, more effective therapeutic strategies are urgently needed. MicroRNAs (miRNAs) have emerged as promising therapeutic tools and targets, as they play significant roles in regulating key cellular processes by suppressing gene expression. However, additive opportunities involving miRNAs have been underexplored. For example, both miR‐34a and miR‐200c individually suppress the development of different types of cancer, but the cellular effects of their combined actions remain unknown. Here, we show that miR‐34a and miR‐ 200c levels are reduced in breast tumors compared to adjacent normal tissues and that this additively predicts poor patient survival. In addition, in cell lines, miR‐34a and miR‐200c additively induce apoptosis and cell cycle arrest, while also inhibiting proliferation, invasion, migration, stemness and epithelial‐to‐mesenchymal transition (EMT). Mechanistically, both miRNA‐34a and miR‐ 200c directly target HIF1‐α and subsequently downregulate VEGFR, MMP9 and CXCR4, although combined miRNA‐34a and miR‐200c delivery suppresses mouse xenograft tumor development as effectively as individual delivery. We establish a model, supported by in vitro and clinical data, which collectively suggest that the co‐delivery of miR‐34a and miR‐200c represents a promising novel therapeutic strategy for breast cancer patients.
- Subjects :
- 0301 basic medicine
cancer stemness
Cell cycle checkpoint
Apoptosis
CXCR4
Metastasis
miR-200c
Mice
0302 clinical medicine
Breast cancer
Cell Movement
Medicine
Genetics (clinical)
apoptosis
Middle Aged
Prognosis
Progression-Free Survival
Gene Expression Regulation, Neoplastic
Matrix Metalloproteinase 9
cell cycle arrest
030220 oncology & carcinogenesis
Heterografts
Female
miR-34a
HIF1-α
Receptors, CXCR4
Epithelial-Mesenchymal Transition
lcsh:QH426-470
MiR‐200c
Breast Neoplasms
HIF1‐α
Malignancy
Article
Cell cycle arrest
03 medical and health sciences
breast cancer
Downregulation and upregulation
Cell Line, Tumor
microRNA
Genetics
Animals
Humans
metastasis
Cancer stemness
Cell Proliferation
business.industry
Cancer
MiR‐34a
Hypoxia-Inducible Factor 1, alpha Subunit
medicine.disease
MicroRNAs
lcsh:Genetics
030104 developmental biology
Cancer research
business
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Mansoori, B, Silvestris, N, Mohammadi, A, Khaze, V, Baghbani, E, Mokhtarzadeh, A, Shanehbandi, D, Derakhshani, A, Duijf, P H G & Baradaran, B 2021, ' Mir-34a and mir-200c have an additive tumor-suppressive effect on breast cancer cells and patient prognosis ', Genes, vol. 12, no. 2, 267 . https://doi.org/10.3390/genes12020267, Genes, Vol 12, Iss 267, p 267 (2021), Genes, Volume 12, Issue 2
- Accession number :
- edsair.doi.dedup.....ed1da4cd3ee00607aad2bdf2eb9d530c