Down-Regulation of MiR-181c-5p Promotes Epithelial-to-Mesenchymal Transition in Laryngeal Squamous Cell Carcinoma via Targeting SERPINE1

Abstract

Laryngeal squamous cell carcinoma (LSCC) arises from the squamous epithelium of the larynx and is associated with a high incidence of cervical lymph node metastasis. MicroRNAs (miRNAs) play a crucial role in the epigenetic regulation of cellular biological processes, including cancer metastasis. However, the molecular mechanisms of specific miRNAs responsible for LSCC metastasis and their clinical significance have yet to be fully elucidated. In this study, LSCC cohort datasets from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) were downloaded and examined by comprehensive bioinformatics analysis, which revealed that upregulation of mRNA <i>SERPINE1</i> and downregulation of <i>miR-181c-5p</i> were associated with unfavorable overall survival. Our analysis showed that <i>SERPINE1</i> expression negatively correlated with the expression level of <i>miR-181c-5p</i> in our LSCC patient samples. Silencing of <i>miR-181c-5p</i> expression promoted cell migration and invasion in cell lines, whereas the overexpression of <i>miR-181c-5p</i> suppressed cell migration and epithelial-to-mesenchymal transition (EMT) through the downregulation of <i>SERPINE1</i>. Further analysis showed that the enhancement effect on EMT and metastasis induced by silencing <i>miR-181c-5p</i> could be rescued through knockdown of <i>SERPINE1</i> expression <i>in vitro</i>. Collectively, our findings indicated that <i>miR-181c-5p</i> acted as an EMT suppressor miRNA by downregulation of <i>SERPINE1</i> in LSCC and offers novel strategies for the prevention of metastasis in LSCC.