MicroRNA-98-HMGA2-POSTN signal pathway reverses epithelial-to-mesenchymal transition in laryngeal squamous cell carcinoma

Abstract

It has been widely considered that reversing epithelial-to-mesenchymal transition (EMT) is a potential access to restrain cancer progression and therapeutic resistance. Here, we aim to uncover the novel mechanisms by which we can reverse EMT and inhibit metastasis in laryngeal squamous cell carcinoma (LSCC). We show that miR-98 is significantly reduced in both LSCC specimens and cell lines. Over-expression of miR-98 inhibits the EMT-related gene expression and metastasis and invasive behavior in LSCC in vitro, as well as reduces lung metastasis in mouse model. In the mechanistically study, miR-98 directly targets HMGA2 in mediating EMT. HMGA2 knock down by si-RNA method declines several EMT-related genes expression and LSCC migration and invasion. In parallel, overexpression of HMGA2 transforms LSCC cells to acquire stem cell-like features. Furthermore, we reveal that HMGA2-mediated EMT is closely linked with the expression of POSTN that inhibits EMT, as a tumor suppressor, by gene profiling analyses. POSTN is transcriptionally repressed by HMGA2. In clinic, the HMGA2 mRNA level is negatively correlated with the miR-98 level in LSCC patient cohort. In conclusion, our study confers a powerful signal: miR-98-HMGA-POSTN in LSCC, which is able to reverse EMT and inhibit metastasis, underlining the therapeutic potential of this signal.

Keywords: Epithelial-To-mesenchymal transition; HMGA; Laryngeal squamous cell carcinoma; POSTN; miR-98.