Long Noncoding RNA WT1-AS Inhibits the Progression of Cervical Cancer by Sponging miR-205.

Abstract

Background: Cervical cancer (CC) is the second frequent cancer of women in developing countries. Plentiful studies proved that long noncoding RNA antisense of the tumor suppressor gene WT1 (WT1-AS) participated in the progression of CC. However, the role of WT1-AS remains unclear. This study investigated the potential mechanisms of WT1-AS in CC. Methods: The expression of WT1-AS and miR-205 were determined by quantitative real-time polymerase chain reaction. The cellular localization of WT1-AS in CC cells was detected by subcellular fractionation assay. The level of epithelial-mesenchymal transition (EMT)-related proteins of N-cadherin, E-cadherin, MMP9, and MMP2 were measured by Western blot. Moreover, cell cycle, apoptosis, migration, and invasion were detected by flow cytometry and transwell assay, respectively. The interrelation between WT1-AS and miR-205 was verified by dual-luciferase reporter and RNA immunoprecipitation assays. The role of WT1-AS in modifying CC growth was identified using xenograft tumor model. Results: WT1-AS was downregulated in cervical tissues and cell lines. WT1-AS was predominantly located in the cytoplasm of CC cells. Upregulation of WT1-AS promoted cell apoptosis, blocked cell cycle, migration, invasion, and EMT in vitro. Moreover, miR-205, as a target gene of WT1-AS, was increased in cervical tissues and cell lines. Besides, miR-205 mimic reversed the effect of WT1-AS upregulation on cell cycle, apoptosis, migration, invasion, and EMT. Also, WT1-AS caused the curb of xenograft tumor growth in vivo. Conclusion: Upregulation of WT1-AS suppressed CC development through sponging miR-205, providing experimental basis for clinical targeted treatment of CC.