MicroRNA-153 inhibits tumor progression in esophageal squamous cell carcinoma by targeting SNAI1
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One of the important mediators of Epithelial to mesenchymal transition (EMT) is the Snail1 protein (encoded by SNAI1) which facilitates transition to mesenchymal state by transcriptionally repressing the epithelial cell marker E-cadherin. Given its central role in EMT and tumor metastasis, the cell has evolved multiple levels of regulatory mechanism at transcriptional, post-transcriptional, and post-translational level to regulate SNAI1 expression. Recently, miR-153 has been shown to regulate SNAI1 expression in hepatocellular carcinoma. The objective of the current study was to determine if SNAI1 expression in esophageal squamous cell carcinoma (ESCC) is regulated by miR-153. Metagenomic analysis of The Cancer Genome Atlas (TCGA) data identified an inverse correlation between miR-153 and SNAI1 expression in ESCC. Our study showed that the expression of miR-153 was noticeably downregulated in the ESCC cell line investigated and tissues, compared with normal esophageal epithelial cells and matched adjacent non-tumorous esophageal tissue. We demonstrated that miR-153 downregulated Snail expression by directly targeting the 3′-untranslated region (3′UTR) of SNAI1, which could be rescued by the use of miR-153 mimic and antagomir in ESCC cell line and normal esophageal epithelial cells, respectively. MiR-153 mimic inhibited the migration and invasion ability of ESCC cells whereas miR-153 antagomir promoted migration and invasion of normal esophageal epithelial cell line. Finally, overexpression of miR-153 in the ESCC cell line significantly attenuated experimental lung metastasis as assessed by tail vein injection in xenograft assay. Cumulatively, our data indicate that suppression of miR-153 dictates SNAI1 upregulation during EMT and metastatic progression of ESCC.
KeywordsEMT SNAI1 ESCC miR-153
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- 3.Sawada G, Niida A, Uchi R, et al. Genomic landscape of esophageal squamous cell carcinoma in a japanese population. Gastroenterology. 2016;150(5):1171–82. doi: 10.1053/j.gastro.2016.01.035