Downregulation of miR-153 contributes to epithelial-mesenchymal transition and tumor metastasis in human epithelial cancer

Abstract

The epithelial-mesenchymal transition (EMT) is a crucial step in epithelial cancer invasion and metastasis. The aims of this study were to investigate and validate unidentified micro RNAs (miRNAs) that regulate EMT and to reveal their clinical relevance in epithelial cancer patients. By applying miRNA array screening in a natural epithelial-mesenchymal phenotype cell line pair and in a transforming growth factor β-induced EMT cell model, we found miR-153 was markedly downregulated in the cells that underwent an EMT. A close association was confirmed between inhibition of miR-153 and the EMT phenotype, as well as the invasive ability of epithelial cancer cells. Ectopic expression of miR-153 in mesenchymal-like cells resulted in an epithelial morphology change with decreased cellular invasive ability. On the contrary, transfection of a miR-153 inhibitor in epithelial-like cells led to a mesenchymal phenotype change. In vivo ectopic expression of miR-153 significantly inhibited tumor cell metastasis formation. Data from the dual-luciferase reporter gene assay showed, for the first time, that SNAI1 and ZEB2 were direct targets of miR-153. Inverse correlations were also observed between miR-153 and SNA1 and ZEB2 levels in oral cancer patients' samples. Furthermore, low expression level of miR-153 was found to be significantly related to metastasis and poor prognosis in oral cancer patients. These data demonstrate that miR-153 is a novel regulator of EMT by targeting SNAI1 and ZEB2 and indicate its potential therapeutic value for reducing cancer metastasis.

miR-200b and Cancer/Testis Antigen CAGE Form a Feedback Loop to Regulate the Invasion and Tumorigenic and Angiogenic Responses of a Cancer Cell Line to Microtubule-targeting Drugs

“…miR-153 is down-regulated in cells that have undergone EMT by TGF␤ and inhibits tumor metastasis and EMT by targeting SNAI1 and ZEB2 (42). It will be interesting to examine the role of miR-153 in angiogenesis, invasion, and the response to microtubule-targeting drugs in relation to CAGE.…”

miR-153 Silencing Induces Apoptosis in the MDA-MB-231 Breast Cancer Cell Line

“…Zhao et al (2013) discovered that transient transfection of miR-153 in glioblastoma stem cells induces apoptosis. Furthermore, low expression level of miR-153 was found to be significantly related to metastasis and poor prognosis in oral cancer patients by targeting SNAI1 and ZEB2 (Xu et al, 2013). Additionally, abnormal downregulation of miR-153 can also be detected in human ovarian tumors and was correlated significantly with advanced clinical stage (Kim et al, 2010).…”

Subpath analysis of each subtype of head and neck cancer based on the regulatory relationship between miRNAs and biological pathways

“…Downregulation of miR-206 was previously found to contribute to laryngeal cancer proliferation and invasion via regulation of VEGF expression (34), while VEGF was reported to be a predictor for HNSCC (35), implying that miR-206 may be an inhibitor for HNSCC. A previous study found that miR-1 inhibited cell proliferation of HNSCC by targeting TAGLN2 (36), and downregulation of miR-153 promoted tumor metastasis in human epithelial cancer by targeting ZEB2 (37). On the other hand, nucleotide biosynthesis is involved with tumor cell growth during cell proliferation (38).…”