A Positive Feedback Loop of lncRNA-PVT1 and FOXM1 Facilitates Gastric Cancer Growth and Invasion

Abstract

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..

Overexpression of LncRNA PVT1 Predicts Advanced Clinicopathological Features and Serves as an Unfavorable Risk Factor for Survival of Patients with Gastrointestinal Cancers

“…A total of 2585 participants were included with a maximum sample size of 593 and a minimum sample size of 30. Among the 15 articles, the digestive system malignancies assessed in these studies included esophageal carcinoma (2 articles) [39, 44], gastric cancer (6 articles) [22, 33, 38, 40-42], colorectal cancer (2 articles) [20, 37], hepatocellular carcinoma (2 articles) [21, 34], pancreatic cancer (3 articles) [35, 36, 43]. Among the eligible articles, one came from Japan [20], one came from Portugal [36] and the rest of 13 articles were came from China [21-22, 33-35, 37-44].…”

“…Another research further explored the biological role of lncRNA PVT1 in GC, and confirmed that lncRNA PVT1 could accelerate cell proliferation through epigenetically regulating p15 and p16 [33]. PVT1 enhanced cancer cell proliferation and invasion in vitro and in vivo , through the positive feedback loop of PVT1-FOXM1, suggesting that PVT1 could be a potential therapeutic target for gastric cancer [40]. …”

Prognostic Significance of LncRNA PVT1 and Its Potential Target Gene Network in Human Cancers: a Comprehensive Inquiry Based Upon 21 Cancer Types and 9972 Cases

“…However, rectum adenocarcinoma (READ), skin cutaneous melanoma (SKCM), and stomach adenocarcinoma (SKAD) in the TCGA dataset were correlated with a good prognosis although the results were not statistically significant; their corresponding HR values were 0.786 (95%CI: 0.379-1.629, P= 0.517) ‚ 0.92 (95%CI: 0.742-1.141, P= 0.449) and 0.912 (95%CI: 0.702-1.183, P= 0.486) , respectively. We reviewed the relevant studies and found that the high PVT1 level was associated with worse outcomes in gastric cancer and colorectal cancer [22, 26, 30, 33, 36] and that there was no corresponding report for melanoma. The inconsistent results in the TCGA and literature studies in these tumors may be caused by sampling error and publication bias.…”

Long Noncoding RNA EGFR-AS1 Promotes Cell Proliferation by Increasing EGFR mRNA Stability in Gastric Cancer

“…EGFR plays an important role in cell migration, proliferation, cell cycle regulation and other physiological processes [7]. EGFR is up-regulated in various cancers including gastric cancer [12,13], and is recognized as oncogenic driver in tumorigenesis. LncRNA EGFR antisense RNA 1 (EGFR-AS1) is a 2.8-kb transcript that transcribes in the antisense strand of EGFR [17,18].…”