MicroRNA-143 is downregulated in breast cancer and regulates DNA methyltransferases 3A in breast cancer cells

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Characterizing prostaglandin E receptor on epithelial–mesenchymal transition and metastasis in TNBC

This journal suppl. entitled: Primary Therapy of Early Breast Cancer: 14th St.Gallen International Breast Cancer ConferencePoster Presentation: P047postprin

Prostaglandin E2 receptor regulates metastasis and stem-cell like properties in triple-negative breast cancer through SCL19A3

Poster Presentation - Tumor and Cell Biology: no. PO188BACKGROUND/PURPOSE: Majority of BRCA1 mutation-associated tumors share pheno-typic similarity to triple-negative breast cancer (TNBC), understanding the biology of TNBC may improve management of these patients. TNBC is associated with increased risk of metastatic disease and poor prognosis. Prostaglandin E (EP) receptors have been associated with tumor metastasis, however, the contribution on cancer stem cell compartment …published_or_final_versio

MiRNA-199A-5P is a biomarker for and regulator of epithelial-mesenchymal transition in triple negative breast cancer patients

Poster presentation: abstract no. 531Objectives: Triple-negative breast cancer (TNBC) accounts for 15-20% of all breast cancer, and is characterized by the absence of estrogen receptor, progesterone receptor and human epidermal growth factor receptor. The lack of targeted therapy is a major obstacle for treating against this aggressive subtype, hence the search of specific biomarkers may use as potential diagnostic marker and perhaps a therapeutic target for TNBC. Methods: Plasma samples from patients with TNBC and non-TNBC were recruited for miRNA profiling. By using miRCURY LNA array containing 730 miRNAs, we compared the differential miRNA expressions in plasma of patient with TNBC (n=5) and non-TNBC (n=5), as well as healthy controls (n=5). Selected miRNAs were further validated in an independent cohort (n=250) using real-time RT-PCR. Functional study of miRNA was also carried out in the cell lines. Results: Microarray data revealed miR-16, miR-21 and miR-199a-5p have differentially expression between TNBC and non-TNBC. We found that miR-16, miR-21 and miR-199a-5p were underexpressed in TNBC cases when compared with healthy controls. Moreover, post-operative expression levels of miR-16, miR-21 and miR-199a-5p were significantly increased than that of pre-operative plasma of TNBC. We then stratified the patients by TNM stage and associate with miRNA expression level. Plasma miR-199a-5p expression in TNBC patients had significant difference when compared with healthy controls (stage I, p<0.002; stage II, p<0.001; stage III, p<0.011). Transfection of miR-199a-5p mimic significantly reduced cell proliferation and restored the epithelial-mesenchymal transition (EMT) markers (E-cadherin, ZEB1 and TWIST2). Conclusions: Our data implicate that miR-199a-5p is a potential marker for discriminating TNBC cases and non-TNBC cases. The association of miR-199a-5p with EMT markers uncovers an important pathway in metastatic breast cancer. This study provides insights for the potential use of miRNA as diagnostic marker and targeted therapy for the treatment of TNBC.link_to_OA_fulltex

Abstract 3105: MiR-199a-5p confers tumor suppressive role by inhibiting stenmness characteristics in triple-negative breast cancers

Poster presentation: abstract no. 3105OBJECTIVES: Triple negative breast cancer (TNBC) is defined by lack of expression in estrogen (ER) and progesterone receptors (PR) as well as human epidermal growth factor receptor 2 (HER2), which accounts for 10-15% of all breast cancers. TNBC is a more aggressive histological subtype with worse prognosis when compared to other subtypes due to limited therapeutic targets for hormonal and HER2 receptors. With limited treatment options and ineffective targeted therapy, there is an urgent need for the development of novel therapeutic targets to treat this malignant form of breast cancer. METHODS: Focused on the previously identified TNBC biomarker miR-199a-5p by our group, cells were transfected with 199a-5p mimic for functional studies. MTT and wound healing assay were performed to investigate the cell proliferation and migration ability. Immunofluorescence staining was introduced to study TWIST1 and E-cadherin expression in miR199a-5p stable transfected cells. Aldehyde dehydrogenase (ALDH) expression level was compared between breast cancers and normal control cases’ plasma by using real-time RT-PCR. We further used ALDH activity assay to evaluate the stem cell population. In vivo study was also carried out in nude mice to study tumorigenicity. RESULTS: Cell proliferation assay showed that overexpression of miR-199a-5p significantly inhibited cell growth (p = 0.0008). Wound healing assay indicated the ectopic expression of miR-199a-5p can inhibit cell migration compared to control group. In miR-199a-5p stable transfected MDA-MB-231 cell line, increased translocation of Twist 1 protein from nucleus to cytoplasm and increased expression of E-cadherin was detected by immunofluorescence staining. ALDH activity assay result indicated that the proportion of ALDH(BR+) cells decreased significantly from 17.21% to 8.95% in the miR-199a-5p transfected cells when compared to the control group (p = 0.0279). Consistent with in vitro study, the well-recognized breast cancer stem-cell marker, ALDH1A, was significantly upregulated in the plasma of breast cancer patients than in healthy controls. Moreover, in vivo study also revealed that stable MDA-MB-231 cell line with ectopic miR199a-5p expression resulted in smaller volume of tumors in nude mice. CONCLUSIONS: Our data implicate that miR-199a-5p plays a tumor suppressive role in the pathogenesis of TNBC, which may due to the inhibition of stemness characteristics in breast cancer cells. These findings suggest that miR-199a-5p involved in TNBC stemness-related features and thus provide insights in development of the novel therapeutic strategies for this highly malignant breast cancer.link_to_OA_fulltex

MiR-199a-5p confers tumor suppressive role by inhibiting stemness characteristics in triple negative breast cancer

Poster presentation: abstract no. 3105OBJECTIVES: Triple negative breast cancer (TNBC) is defined by lack of expression in estrogen (ER) and progesterone receptors (PR) as well as human epidermal growth factor receptor 2 (HER2), which accounts for 10-15% of all breast cancers. TNBC is a more aggressive histological subtype with worse prognosis when compared to other subtypes due to limited therapeutic targets for hormonal and HER2 receptors. With limited treatment options and ineffective targeted therapy, there is an urgent need for the development of novel therapeutic targets to treat this malignant form of breast cancer. METHODS: Focused on the previously identified TNBC biomarker miR-199a-5p by our group, cells were transfected with 199a-5p mimic for functional studies. MTT and wound healing assay were performed to investigate the cell proliferation and migration ability. Immunofluorescence staining was introduced to study TWIST1 and E-cadherin expression in miR199a-5p stable transfected cells. Aldehyde dehydrogenase (ALDH) expression level was compared between breast cancers and normal control cases’ plasma by using real-time RT-PCR. We further used ALDH activity assay to evaluate the stem cell population. In vivo study was also carried out in nude mice to study tumorigenicity. RESULTS: Cell proliferation assay showed that overexpression of miR-199a-5p significantly inhibited cell growth (p = 0.0008). Wound healing assay indicated the ectopic expression of miR-199a-5p can inhibit cell migration compared to control group. In miR-199a-5p stable transfected MDA-MB-231 cell line, increased translocation of Twist 1 protein from nucleus to cytoplasm and increased expression of E-cadherin was detected by immunofluorescence staining. ALDH activity assay result indicated that the proportion of ALDH(BR+) cells decreased significantly from 17.21% to 8.95% in the miR-199a-5p transfected cells when compared to the control group (p = 0.0279). Consistent with in vitro study, the well-recognized breast cancer stem-cell marker, ALDH1A, was significantly upregulated in the plasma of breast cancer patients than in healthy controls. Moreover, in vivo study also revealed that stable MDA-MB-231 cell line with ectopic miR199a-5p expression resulted in smaller volume of tumors in nude mice. CONCLUSIONS: Our data implicate that miR-199a-5p plays a tumor suppressive role in the pathogenesis of TNBC, which may due to the inhibition of stemness characteristics in breast cancer cells. These findings suggest that miR-199a-5p involved in TNBC stemness-related features and thus provide insights in development of the novel therapeutic strategies for this highly malignant breast cancer.link_to_OA_fulltex

A cell-free microRNA as biomarker in triple-negative breast patients

Abstract & poster presentatio