The androgen receptor (AR) regulates progression of renal cell carcinoma (RCC) via a mechanism dependent on VHL status and hypoxia, according to data published in Oncogene.
RCC is associated with inactivation of the von Hippel–Lindau (VHL) suppressor protein, which targets hypoxia-inducible factors HIF-1α and HIF-2α. VHL inactivation is associated with a good prognosis, but the mechanisms of this effect are not well understood. However, hypoxia is known to regulate processes including proliferation, apoptosis, angiogenesis, and tumour invasion. Like VHL, AR is also known to promote RCC progression, most likely via HIF-2α and vascular endothelial growth factor regulation.
Several studies have investigated the role of long noncoding RNAs (lncRNAs) in hypoxia. Thus, a team led by Dr Chawnshang Chang analysed the differential expression of lncRNAs in RCC tissue compared with benign tissue using RCC cell lines that were both positive and negative for VHL expression, under both normoxia and hypoxic conditions.
“Kidney cancer, particularly ccRCC, has been known to implicate hypoxia signalling during its genesis and progression as well as having a clear gender bias,” explains Chang. “We have found that AR can have a positive role in promoting ccRCC progression, but the exact details of AR’s role are not clear.”
LncRNA-SARCC is differentially modulated by hypoxia in a VHL-dependent manner and is physically associated with AR. (a) A schematic illustration of the procedure used to discover and define LncRNAs in RCC.