Abstract
Regional lymph node metastasis and distant metastasis are critical in the prognosis of laryngeal squamous cell carcinoma (LSCC). This study investigated the roles of miR-144-3p and E26 transformation specific-1 (ETS-1) in the invasion and migration of LSCC cells. The effects of miR-144-3p and ETS-1 on FaDu and Hep2 cell growth, migration and invasion were determined. Suppression of ETS-1 by miR-144-3p was confirmed using luciferase assays; the effects of ETS-1 silencing were determined using a xenograft tumor model. The expression of ETS-1 was analyzed in 71 paraffin-embedded tissue biopsies and eight fresh frozen biopsies obtained from LSCC patients. miR-144-3p inhibited the growth, invasion and migration of FaDu and Hep2 cells in part through suppression of epithelial-mesenchymal transition as determined by increased E-cadherin and α-catenin and reduced fibronectin and vimentin expression. Additionally, ETS-1 is a molecular target of miR-144-3p, and silencing ETS-1 expression inhibited FaDu and Hep2 cell invasion and migration as well as reduced Hep2 xenograft tumor volume. In LSCC, the expression of ETS-1 is upregulated with disease progression, and higher ETS-1 expression, which was negatively associated with miR-144-3p levels, adversely corresponded with prognoses. Thus, upregulated ETS-1 levels may promote LSCC metastasis, resulting in poor patient prognosis.
Highlights
Head and neck squamous cell carcinoma (HNSCC) is the sixth most abundant cancer worldwide [1]
We found that the expression of miR-144-3p was downregulated in Laryngeal squamous cell carcinoma (LSCC) [10], which is similar to previous studies [11, 12]
3D cultures transfected with a miR-144-3p inhibitor had a greater number of longer cellular processes as compared to the negative control (NC) group (Figure 2C). These results suggest that miR-144-3p inhibits cell migration, invasion and possibly metastasis in vivo
Summary
Head and neck squamous cell carcinoma (HNSCC) is the sixth most abundant cancer worldwide [1]. MicroRNAs (miRNAs) play important roles in the occurrence and development of human cancers, including HNSCCs [6,7,8,9]. We previously predicted that the transcriptional oncoprotein, E26 transformation specific-1 (ETS-1), is a putative molecular target for miR-144-3p using PicTar, miRanda, and TargetScan [10]. In both acute lymphoblastic leukemia cells and acute myeloid leukemia cells, an ETS-1/Smad complex induces antifolate resistance [14]. Calli et al [17] reported that ETS-1 expression is upregulated in LSCC and may play a role in invasion. These studies may form the basis for further analysis of the predictive potential of analyzing miR-144-3p in LSCC
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