American Association for Cancer Research
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Supplementary figure 1. from A Positive Feedback Loop of lncRNA-PVT1 and FOXM1 Facilitates Gastric Cancer Growth and Invasion

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posted on 2023-03-31, 20:01 authored by Mi-die Xu, Yiqin Wang, Weiwei Weng, Ping Wei, Peng Qi, Qiongyan Zhang, Cong Tan, Shu-juan Ni, Lei Dong, Yusi Yang, Wanrun Lin, Qinghua Xu, Dan Huang, Zhaohui Huang, Yuqing Ma, Wei Zhang, Weiqi Sheng, Xiang Du

(A) Analysis of PVT1 alteration frequency in GC tissues from TCGA data. (B) Kaplan-Meier survival curves in an independent GC subgroup showed that the DFS (n=359) and DSS (n=593) rates of the high PVT1 expression group were significantly higher than that of the low expression group. The hazard ratios (HRs) and P values were calculated with a log-rank test. (C) Kaplan-Meier survival curves of patients with varying PVT1 expression, which were stratified by lymphatic and distant metastasis status. (Upper) DFS of patients with (N1, n=164) or without (N0, n=26) lymphatic metastasis and DSS of patients with (N1, n=164) or without (N0, n=26) lymphatic metastasis; (Below) DFS of patients with (M1, n=24) or without (M0, n=166) distant metastasis and DSS of patients with (M1, n=24) or without (M0, n=166) distant metastasis. The HRs and P values were calculated with log-rank tests. (D) Kaplan-Meier survival curves for patients with PVT1 expression in the independent cohort, stratified by lymphatic and distant metastasis status. The HRs and P values were calculated with log-rank tests.


Science and Technology Commission of Shanghai Municipality

National Natural Science Foundation of China

Hospital Foundation of Fudan University Shanghai Cancer Center

Shanghai Hospital Development Center

Shanghai Key Developing Disciplines

Shanghai Science and Technology Development Fund

Domestic Science and Technology Cooperation



Purpose: 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 tumorigenesis and progression.Experimental Design: The expression level of PVT1 was determined by RT-qPCR analysis in 190 pairs of gastric cancer tissues and adjacent normal gastric mucosa tissues (ANT). The biologic 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 immunoprecipitation 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.Results: The lncRNA PVT1 was significantly upregulated in gastric cancer tissues compared with ANTs. High expression of PVT1 predicted poor prognosis in patients with gastric cancer. PVT1 enhanced gastric cancer cell proliferation and invasion in vitro and in vivo. PVT1 directly bound FOXM1 protein and increased FOXM1 posttranslationally. 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.Conclusions: Our study suggests that PVT1 promotes tumor progression by interacting with FOXM1. PVT1 may be a valuable prognostic predictor for gastric cancer, and the positive feedback loop of PVT1-FOXM1 could be a therapeutic target in pharmacologic strategies. Clin Cancer Res; 23(8); 2071–80. ©2016 AACR.

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