Identification and investigation of metastasis specific miRNAs in breast cancer cells for miRNA replacement therapy

Recent studies have shown that miRNAs can regulate cancer and metastatic processes. The aim of this study was to identify specific metastasis suppressor miRNA through meta-analysis method, which can be used as a therapeutic target in miRNA-based breast cancer therapy to prevent or delay breast cancer metastasis. This study presented the therapeutic ability of the three identified metastasis suppressor miRNAs through in-vitro miRNA replacement therapy. The mimics of "hsa-miR-145-5p", "hsa-miR-143-3p", and "hsa-miR-99A-5p" were transfected into "MDA-MB-231" cell lines. In-vitro cell migration assay was completed for functional analysis of the effect of the replacement therapy. Additionally, since a single miRNA can regulate many genes involved in different signaling pathways, we analyzed the effect of the transfected miRNAs at the transcription level through microarray analysis. Differential expression of selected genes was validated at the protein level by western blot and zymogram. Our results suggest that each of the three metastatic suppressor miRNAs is affecting different biological pathways in tumorigenesis. Also, the therapeutic potentials of "hsa-miR-145-5p", "hsa-miR-143-3p", and "hsa-miR-99a-5p" in breast cancer are observed, showing the tumor-suppressive functionalities. Keywords: miRNA Mimic, Breast Cancer, miRNA Transfection, Western-Blot, miRNA Replacement Therapy, Meta-Analysis, Metastasis.