MiR-448 inhibits the epithelial-mesenchymal transition in breast cancer cells by directly targeting the E-cadherin repressor ZEB1/2. Issue 5 (March 2018)

• Record Type: Journal Article
• Authors: Ma, Peng; Ni, Kan; Ke, Jing; Zhang, Wenyi; Feng, Ying; Mao, Qinsheng
• Is Part Of: Experimental biology and medicine. Volume 243:Issue 5(2018)
• Page Start: 473
• Page End: 480
• Publication Date: 2018-03
• Subjects: Cancer -- cell -- disease -- microRNA -- molecular -- oncogenesis; Physiology -- Periodicals; Biology, Experimental -- Periodicals; Medicine, Experimental -- Periodicals; 610.72
• DOI: 10.1177/1535370218754848
• Languages: English
• ISSNs: 1535-3702

Abstract

Recently, accumulating evidence provides that dysregulation of microRNAs (miRNAs) is considered to play vital roles in tumor progression. Based on microRNA arrays, we found that microRNA-448 (miR-448) was significantly downregulated in breast cancer tissue specimens. In our study, we were in an effort to clarify the function, the direct target gene, and the molecular mechanisms of miR-448 in breast cancer. By quantitative RT–PCR, we analyzed the expression of miR-448 in 16 patients with BC. Overexpression of miR-448 was established by transfecting miR-448-mimics into MDA-MB-231 and MCF-7 cells, methyl thiazolyl- tetrazolium and colony formation assays were performed to evaluate its effects on cell proliferation. We also performed cell migration and invasion assays in breast cells overexpressing miRNA-448. All the results indicated that overexpression of miR-448 in breast cancer cells markedly suppressed cell proliferation, migration, and invasion. Through the quantitative RT–PCR and Western Blots, we also evaluated epithelial–mesenchymal transition. We found that overexpression of miR-448 also downregulated the expression of vimentin, a well-known mesenchymal marker. Meanwhile, the epithelial marker E-cadherin was unregulated, suggesting that miR-448 inhibited epithelial–mesenchymal transition . Bioinformatics assay coupled with Western Blot and luciferase assays revealed that miR-448 directly binds to the 3′UTR of E-cadherin repressor ZEB1/2, resulting in suppression of epithelial–mesenchymal transition in breast cancer cells. Impact statement: In our study, we revealed that miR-448 played a vital role in breast cancer development and we also uncovered the mechanisms of it. Following is the short description of the main findings:miR-448 is downregulated in BC. miR-448 regulates cell proliferation, migration, and invasion in BC. miR-448 specifically regulates ZEB1/2 through binding to the 3′UTR in BC cells. miR-448 inhibits cell migration, invasion, and EMT by targeting to the 3′UTR of ZEB1/2.