Down-Regulation of miR-194-5p for Predicting Metastasis in Breast Cancer Cells

• Published in: International journal of molecular sciences 2021-12, Vol.23 (1), p.325
• Main Authors: Yen, Yu-Ting, Yang, Jou-Chun, Chang, Jiun-Bo, Tsai, Shih-Chang
• Format: Article
• Language: English
• Subjects: Assaying; Base Sequence; Breast cancer; Breast Neoplasms - genetics; Breast Neoplasms - pathology; Cancer therapies; Cell adhesion & migration; Cell Line, Tumor; Cell Movement - genetics; Down-Regulation - genetics; Drug resistance; Enzymes; Estrogens; Female; Gelatin; Gelatinase A; Gelatinase B; Gene expression; Gene Expression Regulation, Neoplastic; Genes; Genomes; Growth factors; Humans; Invasiveness; Kinases; Matrix metalloproteinase; Matrix Metalloproteinase 2 - metabolism; Matrix Metalloproteinase 9 - metabolism; Matrix metalloproteinases; Medical prognosis; Mesenchyme; Metalloproteinase; Metastases; Metastasis; MicroRNAs - genetics; MicroRNAs - metabolism; miRNA; Models, Biological; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasm Proteins - metabolism; Protein synthesis; Proteins; Survival Analysis; Transcription; Tumors; Vimentin; Western blotting; Wound healing; Zonula occludens-1 protein
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms23010325

MicroRNAs (miRNAs), as key negative regulators of gene expression, are closely related to tumor occurrence and progression. miR-194-5p (miR-194-1) has been shown to play a regulatory role in various cancers however, its biological function and mechanism of action in breast cancer have not yet been well explored. In this study, we use the UALCAN and LinkedOmics databases to analyze transcription expression in The Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA). The epithelial-mesenchymal transition status of breast cancer cells was evaluated by wound-healing assay, trans-well assays, and gelatin zymography, while protein expression was assessed by Western blotting. miR-194-5p expression was found to be up-regulated in breast cancer clinical specimens but down-regulated in the triple-negative breast cancer (TNBC) cell line MDA-MB-231 and breast cancer clinical specimens in The Cancer Genome Atlas (TCGA). miR-194-5p significantly inhibited the expression of the epithelial marker ZO-1 and increased the expression of mesenchymal markers, including ZEB-1 and vimentin, in MDA-MB-231 cells. miR-194-5p significantly reduced the gelatin-degrading activity of matrix metalloproteinase-2 (MMP-2) and MMP-9 in zymography assays. In MDA-MB-231 cells and TCGA patient samples, ZEB-1 expression was significantly inversely correlated with miR-194-5p expression. High levels of miR-194-5p were associated with good overall survival. miR-194-5p regulates epithelial-mesenchymal transition (EMT) in TNBC. Our findings suggest that miR-194-5p functions as a tumor biomarker in breast cancer, providing new insights for the study of breast cancer development and metastasis.