Vitamin D receptor upregulates lncRNA TOPORS-AS1 which inhibits the Wnt/β-catenin pathway and associates with favorable prognosis of ovarian cancer
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...
Guardado en:
| Autores principales: | , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Nature Portfolio
2021
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/65ade6c8406f4b738102f26bddc6728e |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| Sumario: | 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 |
|---|