A positive feedback regulatory loop involving the lncRNA PVT1 and HIF-1α in pancreatic cancer
Yiping Zhu, Fang Wu, Weiwei Gui, Nan Zhang, Erik Matro, Linghua Zhu, Daniel Turunen Eserberg, Xihua Lin
Abstract
Extreme hypoxia is among the most prominent pathogenic features of pancreatic cancer (PC). Both the long non-coding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) and hypoxic inducible factor-1α (HIF-1α) are highly expressed in PC patients and play a crucial role in disease progression. Reciprocal regulation involving PVT1 and HIF-1α in PC, however, is poorly understood. Here, we report that PVT1 binds to the HIF-1α promoter and activates its transcription. In addition, we found that PVT1 could bind to HIF-1α and increases HIF-1α post-translationally. Our findings suggest that the PVT1‒HIF-1α positive feedback loop is a potential therapeutic target in the treatment of PC.