Year-end Sale % OFF 
Abstract
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.
Highlights
Breast cancer is the second most prevalent cancer in the USA and is the second most common cause of cancer-related death in this country [1]
Results miR-205 expression in breast cell lines and tissues The levels of miR-205 were measured in five breast cell lines. miR-205 was significantly reduced in BT549, MDAMB-231 and MDA-MB-436 compared to the normal-like MCF10A breast cell line (Figure 1A)
We found a significant reduction of proliferation (Figure 4A) and invasion (Figure 4B) of MDA-MB-231 and BT549 cells treated with HMGB3 small interfering RNA (siRNA) compared to scrambled control siRNA
Summary
Breast cancer is the second most prevalent cancer in the USA and is the second most common cause of cancer-related death in this country [1]. It is estimated that 230,480 women will develop breast cancer in 2011 and 39,520 will die of this disease [2]. Breast cancer is a heterogeneous disease that differs molecularly, biologically and clinically. Breast cancer is commonly classified by the estrogen/progesterone (ER/PR) receptor status and the HER2 (ERBB2) amplification status. Breast cancers that are ER+ and or PR+ are treatable with hormonal therapies such as Tamoxifen, while patients having HER2 amplification respond to receptor tyrosine kinase inhibitors such as Trastuzumab. Triple-negative breast cancer (TNBC) is defined by the absence of ER and PR expression and HER2 amplification
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
