LncRNA-CTS promotes metastasis and epithelial-to-mesenchymal transition through regulating miR-505/ZEB2 axis in cervical cancer

Abstract

Cervical carcinoma (CC) is the second most common cancer in females. In order to improve current anti-metastasis strategies for CC, it is important to improve our understanding of the mechanisms involved in epithelial-to-mesenchymal transition (EMT). This study aimed to elucidate the potential role of a novel long non-coding RNA (lncRNA)-CTS and the mechanisms underlying EMT in CC. The expression levels of lncRNA-CTS and miR-505 were detected using quantitative reverse transcriptase polymerase chain reaction in CC specimens and cells (HeLa, SiHa, Ca-Ski, C-33A, and HT-3). Further experiments including wound scratch and transwell invasion assays, Western blotting, immunofluorescence, and luciferase assays were used to investigate the function of lncRNA-CTS/miR-505/ZEB2 in vitro. In addition, a tumor xenograft model was used to assess the effect of lncRNA-CTS in vivo. The expression levels of lncRNA-CTS and miR-505 were correlated with the metastasis-associated clinicopathological features of CC patients. Moreover, lncRNA-CTS was associated with a poor prognosis in CC patients. In vitro and in vivo experiments, along with gain- and loss-of-function studies, showed that lncRNA-CTS enhanced cell migration, invasion, and the transforming growth factor (TGF)-β1-induced-EMT process. Data also showed that lncRNA-CTS could function as a competing endogenous RNA for miR-505 in CC cells. Further investigations disclosed that ZEB2 was demonstrated as a downstream target of miR-505, and subsequently exerted its metastatic effects via the lncRNA-CTS/miR-505/ZEB2 axis in CC cells. Finally, lncRNA-CTS activated the SMAD/TGF pathway via miR-505 in CC cells. Collectively, our results demonstrate the importance of the lncRNA-CTS/miR-505/ZEB2 axis in CC. LncRNA-CTS can predispose CC patients to metastases and may represent a promising therapeutic target for CC.

Keywords: Cervical cancer; Epithelial-mesenchymal transition (EMT); Long non-coding RNA; TGF/SMAD signal pathway; Transforming growth factor-β1(TGF-β1).