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A Positive Feedback Loop of lncRNA- PVT1 and FOXM1 Facilitates Gastric Cancer Growth and Invasion
Ist Teil von
Clinical cancer research, 2017-04, Vol.23 (8), p.2071-2080
Ort / Verlag
United States: American Association for Cancer Research Inc
Erscheinungsjahr
2017
Quelle
MEDLINE
Beschreibungen/Notizen
The long, noncoding RNA (lncRNA)
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
in gastric cancer tumorigenesis and progression.
The expression level of
was determined by RT-qPCR analysis in 190 pairs of gastric cancer tissues and adjacent normal gastric mucosa tissues (ANT). The biologic functions of
were assessed by
and
functional experiments. RNA protein pull-down assays and LS/MS mass spectrometry analysis were performed to detect and identify the
interacting protein FOXM1. Protein-RNA immunoprecipitation assays were conducted to examine the interaction of FOXM1 and
Chromatin immunoprecipitation (ChIP) and luciferase analyses were utilized to identify the binding site of FOXM1 on the
promoter.
The lncRNA
was significantly upregulated in gastric cancer tissues compared with ANTs. High expression of
predicted poor prognosis in patients with gastric cancer.
enhanced gastric cancer cell proliferation and invasion
and
directly bound FOXM1 protein and increased FOXM1 posttranslationally. Moreover,
is also a FOXM1-responsive lncRNA, and FOXM1 directly binds to the
promoter to activate its transcription. Finally,
fulfilled its oncogenic functions in a FOXM1-mediated manner.
Our study suggests that
promotes tumor progression by interacting with FOXM1.
may be a valuable prognostic predictor for gastric cancer, and the positive feedback loop of
-FOXM1 could be a therapeutic target in pharmacologic strategies.
.