Tumor recurrence and metastasis result in an unfavorable prognosis for cancer patients. Recent studies have suggested that specific microRNAs (miRNAs) may play important roles in the development of cancer cells. However, prognostic markers and the outcome prediction of the miRNA signature in breast cancer patients have not been comprehensively assessed. The aim of this study was to identify miRNA biomarkers relating to clinicopathological features and outcome of breast cancer. A miRNA microarray analysis was performed on breast tumors of different lymph node metastasis status and with different progression signatures, indicated by overexpression of cyclin D1 and β-catenin genes, to identify miRNAs showing a significant difference in expression. The functional interaction between the candidate miRNA, miR-30a, and the target gene, Vim, which codes for vimentin, a protein involved in epithelial-mesenchymal transition, was examined using the luciferase reporter assay, western blotting, and migration and invasion assays. The association between the decreased miR-30a levels and breast cancer progression was examined in a survival analysis. miR-30a negatively regulated vimentin expression by binding to the 3'-untranslated region of Vim. Overexpression of miR-30a suppressed the migration and invasiveness phenotypes of breast cancer cell lines. Moreover, reduced tumor expression of miR-30a in breast cancer patients was associated with an unfavorable outcome, including late tumor stage, lymph node metastasis, and worse progression (mortality and recurrence) (p < 0.05). In conclusion, these findings suggest a role for miR-30a in inhibiting breast tumor invasiveness and metastasis. The finding that miR-30a downmodulates vimentin expression might provide a therapeutic target for the treatment of breast cancer.
Abstract:One of the persistent challenges confronting tissue engineering is the lack of intrinsic microvessels for the transportation of nutrients and metabolites. An artificial microvascular system could be a feasible solution to this problem. In this study, the femtosecond laser ablation technique was implemented for the fabrication of pillared microvessel scaffolds of polylactic-co-glycolic acid (PLGA). This novel scaffold facilitates implementation of the conventional cell seeding process. The progress of cell growth can be observed in vitro by optical microscopy. The problems of becoming milky or completely opaque with the conventional PLGA scaffold after cell seeding can be resolved. In this study, PLGA microvessel scaffolds consisting of 47 µm × 80 µm pillared branches were produced. Results of cell culturing of bovine endothelial cells demonstrate that the cells adhere well and grow to surround each branch of the proposed pillared microvessel networks.
In this study, a novel method for the fabrication of hollow three-dimensional (3D) poly(lactic-co-glycolic acid) (PLGA) microvessel scaffolds is proposed. In this novel fabrication method, a salt ingot, which was used as a temporary frame to define the shape of the desired scaffold, was fabricated by extrusion molding. The salt ingot was immersed in a PLGA solution and the PGLA enveloped the ingot entirely. The femtosecond laser ablation technique was used for ablating the desired pattern on the PLGA layer and then the salt ingot was completely dissolved in distilled deionized water. A hollow 3D PLGA scaffold was obtained using this process on which bovine endothelial cells (BECs) were then cultured. Scanning electron microscopy (SEM) and fluorescent images of the cell seeding demonstrate that the BECs adhered and grew well on both the side-wall of the branches and the surroundings of each branch.
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