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Epigenetic silencing of ITGA2 by MiR-373 promotes cell migration in breast cancer.
- Source :
-
PloS one [PLoS One] 2015 Aug 10; Vol. 10 (8), pp. e0135128. Date of Electronic Publication: 2015 Aug 10 (Print Publication: 2015). - Publication Year :
- 2015
-
Abstract
- The loss of ITGA2 plays an important role in cancer metastasis in several solid cancers. However, the molecular mechanism of ITGA2 loss in primary cancers remains unclear. In this study, we found that a lower ITGA2 protein level was observed in breast cancers compared to adjacent non-cancerous breast tissues. Interestingly, the reduction degree of ITGA2 at the protein level was far more than that at the mRNA level. We further showed that the translation of ITGA2 mRNA was directly inhibited by miR-373 through binding to ITGA2-3'UTR. Silencing of ITGA2 detached cell-cell interactions, induced the deploymerization of stress fiber F-actin and stimulated cancer cell migration, similar to the effect of miR-373 over-expression. The co-expression of ITGA2, not ITGA2-3'UTR, could abrogate miR-373-induced cancer cell migration because that the expression of ITGA2-3'UTR was inhibited by co-transfected miR-373. ITGA2 protein level was inversely associated with miR-373 level in breast cancers (r = -0.663, P<0.001). 73.33% of breast cancer patients with high miR-373 and low ITGA2 expression exhibited the lymph node-positive metastases. Together, our results show that epigenetic silencing of ITGA2 by miR-373 stimulates breast cancer migration, and miR-373high/ITGA2low may be as a prognosis biomarker for breast cancer patients.
- Subjects :
- Actins chemistry
Actins genetics
Actins metabolism
Adult
Aged
Breast Neoplasms metabolism
Cell Movement
Cell Proliferation
Female
Genes, Reporter
Humans
Integrin alpha2 metabolism
Luciferases genetics
Luciferases metabolism
Lymphatic Metastasis
MCF-7 Cells
MicroRNAs metabolism
Middle Aged
Signal Transduction
3' Untranslated Regions
Breast Neoplasms genetics
Gene Expression Regulation, Neoplastic
Gene Silencing
Integrin alpha2 genetics
MicroRNAs genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 10
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 26258411
- Full Text :
- https://doi.org/10.1371/journal.pone.0135128