Articles by Ana Clara P. Azevedo-Pouly in JoVE
Other articles by Ana Clara P. Azevedo-Pouly on PubMed
MicroRNA Replacement Therapy for Cancer Pharmaceutical Research. Dec, 2011 | Pubmed ID: 21879389 MicroRNA are small noncoding RNAs that translationally repress their target messenger RNAs. Many microRNAs are expressed at reduced levels in tumors. microRNAs with reduced expression in cancer often regulate oncogenes, resulting in enhanced tumor growth. One therapeutic option is to restore microRNA levels in the tumor to that of the non-diseased tissue. This is possible by delivering microRNA to the tumor in the form of an oligonucleotide mimic or by expressing the microRNA in the cancer using a gene vector. This article surveys the field of oligonucleotide mimics and gene vector approaches to restore microRNA levels in tumors and reviews the literature on experimental and pre-clinical studies that have used these approaches to treat cancer.
Tumor Suppressive Function of Mir-205 in Breast Cancer is Linked to HMGB3 Regulation PloS One. 2013 | Pubmed ID: 24098490 Identifying targets of dysregulated microRNAs (miRNAs) will enhance our understanding of how altered miRNA expression contributes to the malignant phenotype of breast cancer. The expression of miR-205 was reduced in four breast cancer cell lines compared to the normal-like epithelial cell line MCF10A and in tumor and metastatic tissues compared to adjacent benign breast tissue. Two predicted binding sites for miR-205 were identified in the 3' untranslated region of the high mobility group box 3 gene, HMGB3. Both dual-luciferase reporter assay and Western blotting confirmed that miR-205 binds to and regulates HMGB3. To further explore miR-205 targeting of HMGB3, WST-1 proliferation and in vitro invasion assays were performed in MDA-MB-231 and BT549 cells transiently transfected with precursor miR-205 oligonucleotide or HMGB3 small interfering RNA (siRNA). Both treatments reduced the proliferation and invasion of the cancer cells. The mRNA and protein levels of HMGB3 were higher in the tumor compared to adjacent benign specimens and there was an indirect correlation between the expression of HMGB3 mRNA and patient survival. Treatment of breast cancer cells with 5-Aza/TSA derepressed miR-205 and reduced HMGB3 mRNA while knockdown of the transcriptional repressor NRSF/REST, reduced miR-205 and increased HMGB3. In conclusion, regulation of HMGB3 by miR-205 reduced both proliferation and invasion of breast cancer cells. Our findings suggest that modulating miR-205 and/or targeting HMGB3 are potential therapies for advanced breast cancer.