Scientific Reports (Apr 2021)

Vitamin D receptor upregulates lncRNA TOPORS-AS1 which inhibits the Wnt/β-catenin pathway and associates with favorable prognosis of ovarian cancer

  • Yuanyuan Fu,
  • Dionyssios Katsaros,
  • Nicoletta Biglia,
  • Zhanwei Wang,
  • Ian Pagano,
  • Marcus Tius,
  • Maarit Tiirikainen,
  • Charles Rosser,
  • Haining Yang,
  • Herbert Yu

DOI
https://doi.org/10.1038/s41598-021-86923-7
Journal volume & issue
Vol. 11, no. 1
pp. 1 – 14

Abstract

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Abstract 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