摘要:Long non-coding RNAs (lncRNAs) have important biological functions, but their involvement in ovarian cancer remains elusive. We analyzed high-throughput data to identify lncRNAs associated with ovarian cancer outcomes. Our search led to the discovery of lncRNA
TOPORS Antisense RNA 1 (
TOPORS-AS1). Patients with high
TOPORS-AS1 expression had favorable overall survival compared to low expression. This association was replicated in our study and confirmed by meta-analysis. In vitro experiments demonstrated that overexpressing
TOPORS-AS1 in ovarian cancer cells suppressed cell proliferation and inhibited aggressive cell behaviors, including migration, invasion, and colony formation. Analysis of tumor cell transcriptomes indicated
TOPORS-AS1′s influence on the Wnt/β-catenin signaling. Additional experiments revealed that
TOPORS-AS1 increased the phosphorylation of β-catenin and suppressed the expression of
CTNNB1, disrupting the Wnt/β-catenin pathway. Our experiments further discovered that vitamin D receptor (VDR) upregulated
TOPORS-AS1 expression and that inhibition of β-catenin by
TOPORS-AS1 required a RNA binding protein, hnRNPA2B1 (heterogeneous nuclear ribonucleoprotein A2B1). Taken together, these findings suggest that
TOPORS-AS1 may behave like a tumor suppressor in ovarian cancer through interrupting the Wnt/β-catenin signaling and that VDR upregulates the expression of
TOPORS-AS1. Assessing
TOPORS-AS1 expression in ovarian cancer may help predict disease prognosis and develop treatment strategy