Silencing of Long Non-coding RNA SMAD5-AS1 Reverses Epithelial Mesenchymal Transition in Nasopharyngeal Carcinoma via microRNA-195-Dependent Inhibition of SMAD5

Abstract

Long non-coding RNAs (lncRNAs) have gained widespread attention in recent years as a key regulator of diverse biological processes, but the knowledge of the mechanisms by which they act is still very limited. Differentially expressed lncRNA SMAD5 antisense RNA 1 (SMAD5-AS1) in nasopharyngeal carcinoma (NPC) and normal samples shown by <i>in silico</i> analyses were selected as the main subject, and then microRNA-195 (miR-195) was suggested to bind to SMAD5-AS1 and SMAD5. Therefore, the purpose of the present study was to investigate the effects of SMAD5-AS1/miR-195/SMAD5 on epithelial-mesenchymal transition (EMT) in NPC cells. High expression of SMAD5-AS1 and SMAD5 but low miR-195 expression was determined in NPC tissues and NPC cell lines by RT-qPCR and western blot analysis. SMAD5-AS1 could upregulate SMAD5 expression by competitively binding to miR-195 in NPC cells. Loss- and gain-of-function investigations were subsequently conducted in NPC cells (CNE-2 and CNE-1) to explore the role of SMAD5-AS, miR-195 and SMAD5 in NPC progression by assessing cellular biological functions and tumorigenic ability <i>in vivo</i> as well as determining the expression of EMT markers. Downregulation of SMAD5-AS1 or SMAD5 or overexpression of miR-195 led to inhibited NPC cell proliferation, invasion and migration and reversed EMT, enhanced apoptosis <i>in vitro</i> as well as restrained tumor growth <i>in vivo</i>. In conclusion, our findings indicate that silencing of lncRNA SMAD5-AS1 induces the downregulation of SMAD5 by miR-195, eventually repressing EMT in NPC. Hence, SMAD5-AS1 may represent a potential therapeutic target for NPC intervention.