Long non-coding RNA WT1-AS inhibits cell aggressiveness via miR-203a-5p/FOXN2 axis and is associated with prognosis in cervical cancer

S.-G. Dai, L.-L. Guo, X. Xia, Y. Pan

Department of Obstetrics and Gynecology, Hangzhou Red Cross Hospital, Hangzhou, Zhejiang, China. yuanpanypan@163.com

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• Oncology

OBJECTIVE: Substantial evidence has demonstrated that long non-coding RNAs (lncRNAs) play pivotal roles in tumorigenesis and tumor progression. The lncRNA Wilms tumor 1 Antisense RNA (WT1-AS) is a potential tumor suppressor in some types of cancers. The objective of this study was to evaluate the biological roles of WT1-AS in cervical cancer.

PATIENTS AND METHODS: The Cancer Genome Atlas (TCGA) was used to identify differentially expressed lncRNAs in cervical carcinoma. The level of lncRNA WT1-AS in cervical carcinoma tissues and cell lines was determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The lentiviral vector encoding WT1-AS (LV-WT1-AS) or miR-203a-5p mimic was transfected into cervical carcinoma cells. Cell Counting Kit-8 (CCK-8), wound healing and transwell invasion assays were applied to assess the role of WT1-AS in cervical cancer cell growth and migration. WT1-AS directly bound to miR-203a-5p was confirmed using Luciferase reporter assay. The level of forkhead box N2 (FOXN2) was assessed by quantitative Real Time-Polymerase Chain Reaction analysis. A xenograft model was constructed to explore the role of WT1-AS in cervical cancer cell growth in vivo.

RESULTS: WT1-AS was down-regulated in both cervical cancer tissues and cell lines. Functional analyses indicated that the over-expression of WT1-AS remarkably inhibited cervical carcinoma cell growth, migration and invasion. The results of the Luciferase reporter assays verified that miR-203a-5p is a direct target of WT1-AS. Moreover, FOXN2 was identified as a direct target gene of miR-203a-5p, and the up-regulation of miR-203a-5p reversed the inhibitory effects of WT1-AS in cervical cancer cells.

CONCLUSIONS: Our results demonstrated that WT1-AS was under-expressed in cervical carcinoma and suppresses cervical cancer cell growth and aggressiveness via a miR-203a-5p/FOXN2 axis.

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