Long noncoding RNA FEZF1-AS1 indicates a poor prognosis of gastric cancer and promotes tumorigenesis via activation of Wnt signaling pathway

Wu, Xiaoli; Zhang, Peichen; Zhu, Hua; Shi, Li; Chen, Xiangjian; Shi, Lingyan

doi:10.1016/j.biopha.2017.11.113

Cited by 71 publications

(68 citation statements)

References 20 publications

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“…39 Downregulation of FEZF1-AS1 was shown to suppress activation of the Wnt/b-catenin signaling pathway in GC, and could therefore be used as a new biomarker for the treatment of GC. 40 Together with our results, these data support the view that the Wnt signaling pathway is closely related to GC. Although we have demonstrated that VCAN expression is a potential independent molecular marker for the diagnosis and prognosis in GC, the major limitations of our study should be noted.…”

Section: Discussionsupporting

confidence: 90%

High expression of VCAN is an independent predictor of poor prognosis in gastric cancer

Han

et al. 2020

J Int Med Res

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Objective: Versican (VCAN) has been reported as a potential biomarker in some cancers. However, its role in gastric cancer (GC) is poorly understood. Methods: Associations between clinical variables and VCAN were assessed. The diagnostic value of VCAN expression in GC patients was determined through receiver operating characteristic (ROC) curve analysis. Cox regression and the Kaplan-Meier method were used to explore clinicopathologic factors related to overall survival in GC patients. The Gene Expression Omnibus and the Human Protein Atlas were used for further validation. Gene set enrichment analysis (GSEA) was performed using The Cancer Genome Atlas dataset. Results: High expression of VCAN was associated with high stage and T classification in GC. The area under the ROC curve was 0.853. Patients with high VCAN expression had worse prognoses than those with low VCAN expression. Multivariate analysis showed that VCAN was an independent risk factor for overall survival in both cohorts. GSEA identified pathways involved in cancer, ECM-receptor interaction, Wnt signaling, T cell receptor signaling, and chemokine signaling as differentially enriched in GCs with high VCAN expression. Conclusion: We demonstrated that VCAN is expressed at high levels in GC, and represents a potential independent molecular marker for diagnosis and prognosis of GC.

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Section: Discussionsupporting

confidence: 90%

High expression of VCAN is an independent predictor of poor prognosis in gastric cancer

Han

et al. 2020

J Int Med Res

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“…FEZF1-AS1 is located on the opposite strand of FEZF1 on chromosome 7. FEZF1-AS1 acts as an oncogene in gastric cancer by suppressing p21 expression or activating Wnt signaling pathway (26,29). The oncogenic roles of FEZF1-AS1 were also observed in lung cancer (30) and colorectal cancer (25).…”

Section: Discussionmentioning

confidence: 95%

LncRNA–FEZF1-AS1 Promotes Tumor Proliferation and Metastasis in Colorectal Cancer by Regulating PKM2 Signaling

Bian

Zhang

et al. 2018

Clinical Cancer Research

246

220

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Long non-coding RNAs (lncRNAs) play key roles in human cancers. Here, FEZF1-AS1, a highly overexpressed lncRNA in colorectal cancer, was identified by lncRNA microarrays. We aimed to explore the roles and possible molecular mechanisms of FEZF1-AS1 in colorectal cancer. LncRNA expression in colorectal cancer tissues was measured by lncRNA microarray and qRT-PCR. The functional roles of FEZF1-AS1 in colorectal cancer were demonstrated by a series of and experiments. RNA pull-down, RNA immunoprecipitation and luciferase analyses were used to demonstrate the potential mechanisms of FEZF1-AS1. We identified a series of differentially expressed lncRNAs in colorectal cancer using lncRNA microarrays, and revealed that FEZF1-AS1 is one of the most overexpressed. Further validation in two expanded colorectal cancer cohorts confirmed the upregulation of FEZF1-AS1 in colorectal cancer, and revealed that increased FEZF1-AS1 expression is associated with poor survival. Functional assays revealed that FEZF1-AS1 promotes colorectal cancer cell proliferation and metastasis. Mechanistically, FEZF1-AS1 could bind and increase the stability of the pyruvate kinase 2 (PKM2) protein, resulting in increased cytoplasmic and nuclear PKM2 levels. Increased cytoplasmic PKM2 promoted pyruvate kinase activity and lactate production (aerobic glycolysis), whereas FEZF1-AS1-induced nuclear PKM2 upregulation further activated STAT3 signaling. In addition, PKM2 was upregulated in colorectal cancer tissues and correlated with FEZF1-AS1 expression and patient survival. Together, these data provide mechanistic insights into the regulation of FEZF1-AS1 on both STAT3 signaling and glycolysis by binding PKM2 and increasing its stability. .

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“…FEZF1‐AS1 is located on chromosome 7 on the opposite strand of FEZF1. FEZF1‐AS1 acts as an oncogene in gastric cancer by activating Wnt signalling pathway or suppressing p21 expression . The oncogenic roles of FEZF1‐AS1 were also observed in colorectal cancer and lung cancer .…”

Section: Discussionmentioning

confidence: 97%

Long non‐coding RNA FEZF1‐AS1 induced progression of ovarian cancer via regulating miR‐130a‐5p/SOX4 axis

Sun

Gao

Xuan

et al. 2020

J Cellular Molecular Medi

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Emerging studies have revealed the critical role of long non‐coding RNAs (lncRNAs) in epithelial ovarian cancer (EOC) development and progression. Till now, the roles and potential mechanisms regarding FEZF1 antisense RNA 1 (FEZF1‐AS1) within ovarian cancer (OC) remain unclear. The objective of this study was to uncover the biological function and the underlying mechanism of LncRNA FEZF1‐AS1 in OC progression. FEZF1‐AS1 expression levels were studied in cell lines and tissues of human ovarian cancer. In vitro studies were performed to evaluate the impact of FEZF1‐AS1 knock‐down on the proliferation, invasion, migration and apoptosis of OC cells. Interactions of FEZF1‐AS1 and its target genes were identified by luciferase reporter assays. Our data showed overexpression of FEZF1‐AS1 in OC cell lines and tissues. Cell migration, proliferation, invasion, wound healing and colony formation were suppressed by silencing of FEZF1‐AS1. In contrast, cell apoptosis was promoted by FEZF1‐AS1 knock‐down in vitro. Furthermore, online bioinformatics analysis and tools suggested that FEZF1‐AS1 directly bound to miR‐130a‐5p and suppressed its expression. Moreover, the inhibitory effects of miR‐130a‐5p on the OC cell growth were reversed by FEZF1‐AS1 overexpression, which was associated with the increase in SOX4 expression. In conclusion, our results revealed that FEZF1‐AS1 promoted the metastasis and proliferation of OC cells by targeting miR‐130a‐5p and its downstream SOX4 expression.

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Long noncoding RNA FEZF1-AS1 indicates a poor prognosis of gastric cancer and promotes tumorigenesis via activation of Wnt signaling pathway

Cited by 71 publications

References 20 publications

High expression of VCAN is an independent predictor of poor prognosis in gastric cancer

High expression of VCAN is an independent predictor of poor prognosis in gastric cancer

LncRNA–FEZF1-AS1 Promotes Tumor Proliferation and Metastasis in Colorectal Cancer by Regulating PKM2 Signaling

Long non‐coding RNA FEZF1‐AS1 induced progression of ovarian cancer via regulating miR‐130a‐5p/SOX4 axis

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