Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 404332, Taiwan.
Drug Development Center, Institute of New Drug Development, Institute of Biomedical Sciences, China Medical University, Taichung 404332, Taiwan.
Int J Mol Sci. 2021 Dec 28;23(1):325. 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.
微小 RNA（miRNA）作为基因表达的关键负调控因子，与肿瘤的发生和发展密切相关。miR-194-5p（miR-194-1）在各种癌症中发挥调节作用，但其在乳腺癌中的生物学功能和作用机制尚未得到充分探索。在本研究中，我们使用 UALCAN 和 LinkedOmics 数据库分析了癌症基因组图谱乳腺浸润性癌（TCGA-BRCA）中的转录表达。通过划痕愈合试验、Transwell 试验和明胶酶谱分析评估乳腺癌细胞的上皮-间充质转化状态，通过 Western blot 检测蛋白表达。结果发现，miR-194-5p 在乳腺癌临床标本中表达上调，但在三阴性乳腺癌（TNBC）细胞系 MDA-MB-231 和癌症基因组图谱（TCGA）中的乳腺癌临床标本中表达下调。miR-194-5p 显著抑制 MDA-MB-231 细胞中上皮标志物 ZO-1 的表达，增加间充质标志物 ZEB-1 和波形蛋白的表达。miR-194-5p 显著降低明胶酶谱分析中基质金属蛋白酶-2（MMP-2）和 MMP-9 的降解活性。在 MDA-MB-231 细胞和 TCGA 患者样本中，ZEB-1 的表达与 miR-194-5p 的表达呈显著负相关。高水平的 miR-194-5p 与良好的总生存期相关。miR-194-5p 调节 TNBC 中的上皮-间充质转化（EMT）。我们的研究结果表明，miR-194-5p 在乳腺癌中作为肿瘤标志物发挥作用，为乳腺癌发生和转移的研究提供了新的见解。
