Androgen receptor promotes renal cell carcinoma (RCC) vasculogenic mimicry (VM) via altering TWIST1 nonsense-mediated decay through lncRNA-TANAR
Open Access
- 28 January 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Oncogene
- Vol. 40 (9), 1674-1689
- https://doi.org/10.1038/s41388-020-01616-1
Abstract
While the androgen receptor (AR) may influence the progression of clear cell renal cell carcinoma (ccRCC), its role to impact vasculogenic mimicry (VM) to alter the ccRCC progression and metastasis remains obscure. Here, we demonstrated that elevated AR expression was positively correlated with tumor-originated vasculogenesis in ccRCC patients. Consistently, in vitro research revealed AR promoted VM formation in ccRCC cell lines via modulating lncRNA-TANAR/TWIST1 signals. Mechanism dissection showed that AR could increase lncRNA-TANAR (TANAR) expression through binding to the androgen response elements (AREs) located in its promoter region. Moreover, we found that TANAR could impede nonsense-mediated mRNA decay (NMD) of TWIST1 mRNA by direct interaction with TWIST1 5′UTR. A preclinical study using in vivo mouse model with orthotopic xenografts of ccRCC cells further confirmed the in vitro data. Together, these results illustrated that AR-mediated TANAR signals might play a crucial role in ccRCC VM formation and metastasis, and targeting this newly identified AR/TANAR/TWIST1 signaling may help in the development of a novel anti-angiogenesis therapy to better suppress the ccRCC progression.Keywords
Funding Information
- U.S. Department of Health & Human Services | National Institutes of Health (NIH grant (CA155477))
This publication has 60 references indexed in Scilit:
- Pazopanib versus Sunitinib in Metastatic Renal-Cell CarcinomaThe New England Journal of Medicine, 2013
- Promotion of tumor cell metastasis and vasculogenic mimicry by way of transcription coactivation by Bcl-2 and Twist1: A study of hepatocellular carcinomaJournal of Hepatology, 2011
- lncRNAs transactivate STAU1-mediated mRNA decay by duplexing with 3′ UTRs via Alu elementsNature, 2011
- Upf1 ATPase-Dependent mRNP Disassembly Is Required for Completion of Nonsense- Mediated mRNA DecayCell, 2010
- Tumor-induced upregulation of Twist, Snail, and Slug represses the activity of the human VE-cadherin promoterArchives of Biochemistry and Biophysics, 2009
- The NMD mRNA surveillance pathway downregulates aberrant E-cadherin transcripts in gastric cancer cells and in CDH1 mutation carriersOncogene, 2008
- Human RISC Couples MicroRNA Biogenesis and Posttranscriptional Gene SilencingCell, 2005
- Human Argonaute2 Mediates RNA Cleavage Targeted by miRNAs and siRNAsMolecular Cell, 2004
- Vasculogenic mimicry and tumour-cell plasticity: lessons from melanomaNature Reviews Cancer, 2003
- Vascular Channel Formation by Human Melanoma Cells in Vivo and in Vitro: Vasculogenic MimicryThe American Journal of Pathology, 1999