The long noncoding RNA (lncRNA) PVT1 is an important epigenetic regulator with a critical role in human tumors. Here, we aimed to investigate the clinical application and the potential molecular mechanisms of PVT1 in gastric cancer (GC) tumorigenesis and progression.

The expression level of PVT1 was determined by RT-qPCR analysis in 190 pairs of GC tissues and adjacent normal gastric mucosa tissues (ANTs). The biological functions of PVT1 were assessed by in vitro and in vivo functional experiments. RNA-protein pull-down assays and LS/MS mass spectrometry analysis were performed to detect and identify the PVT1-interacting protein FOXM1. Protein-RNA immunoprecipitaion (RIP) assays were conducted to examine the interaction of FOXM1 and PVT1. Chromatin immunoprecipitation (ChIP) and luciferase analyses were utilized to identify the binding site of FOXM1 on the PVT1 promoter.

The lncRNA PVT1 was significantly upregulated in GC tissues compared with ANTs. High expression of PVT1 predicted poor prognosis in GC patients. PVT1 enhanced GC cell proliferation and invasion in vitro and in vivo. PVT1 directly bound FOXM1 protein and increased FOXM1 post-translationally. Moreover, PVT1 is also a FOXM1-responsive lncRNA, and FOXM1 directly binds to the PVT1 promoter to activate its transcription. Finally, PVT1 fulfilled its oncogenic functions in a FOXM1-mediated manner.

Our study suggests that PVT1 promotes tumor progression by interacting with FOXM1. PVT1 may be a valuable prognostic predictor for GC, and the positive feedback loop of PVT1-FOXM1 could be a therapeutic target in pharmacological strategies.