Dataset Information

Significance of Circular FAT1 as a Prognostic Factor and Tumor Suppressor for Esophageal Squamous Cell Carcinoma.

ABSTRACT:

Background

Circular RNA is a novel endogenous non-coding RNA with a stable loop structure, and theories for its biogenesis and usefulness as a biomarker in various cancers have been proposed. The present study investigated the significance of circular FAT1 (circFAT1) as a novel biomarker in esophageal squamous cell carcinoma (ESCC).

Method

CircFAT1 expression levels were measured in ESCC cell lines and the effects of downregulating circFAT1 on cell migration and invasion were examined using a transwell assay. The functions of miR-548g, which will be sponged by circFAT1, were assessed. Furthermore, the expression of circFAT1 was evaluated in 51 radically resected ESCC tissue samples using quantitative reverse transcription polymerase chain reaction (qRT-PCR). The relationships between circFAT1 expression, clinicopathological factors, and patient prognosis were analyzed.

Results

CircFAT1 expression levels were significantly lower in tumor tissue than in adjacent non-tumorous mucosal tissue (p = 0.01). The downregulation of circFAT1 expression promoted ESCC cell migration and invasive ability, but not proliferation. The expression of miR-548g was upregulated by the downregulation of circFAT1. The overexpression of miR-548g also promoted ESCC cell migration and invasion. Recurrence-free survival (p = 0.02) and cancer-specific survival (p = 0.04) rates were significantly higher in patients with elevated circFAT1 expression levels.

Conclusion

The expression level of circFAT1 is a novel prognostic marker in ESCC patients. New treatment strategies may be developed using the tumor suppressive functions of circFAT1.

SUBMITTER: Takaki W

PROVIDER: S-EPMC8591040 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The present authors previously identified a novel candidate tumor suppressor gene, zinc finger protein 750 (ZNF750), in esophageal squamous cell carcinoma (ESCC) (1). The present study aimed to clarify the clinical significance of ZNF750 expression in ESCC. The association between ZNF750 DNA mutation status and the mRNA expression was examined by whole exome sequence analysis and quantitative reverse transcription polymerase chain reaction (RT-qPCR). The expression of ZNF750 in 76 patients with ESCC (Kyushu University Beppu Hospital) was measured using immunohistochemistry and RT-qPCR. Using this dataset, the association between ZNF750 mRNA expression and clinicopathological factors was examined. Additionally, survival analysis was performed using datasets from the Kyushu University Beppu Hospital and The Cancer Genome Atlas (TCGA). The biological effects of ZNF750 expression were explored using gene set enrichment analysis (GSEA) and were validated using datasets from the Cancer Cell Line Encyclopedia (CCLE) and the Kyushu University Beppu Hospital. ZNF750 expression analyses demonstrated that ZNF750 mRNA expression was lower in patients with the DNA mutations compared with those without the mutations (P<0.05), and ZNF750 expression was downregulated in tumor tissues compared with normal tissues (P<0.00005). In the clinicopathological analysis, the low ZNF750 expression group exhibited a higher incidence of undifferentiated histology (P<0.05) compared with the high expression group. The low ZNF750 expression group exhibited a poorer prognosis in the Kyushu and TCGA datasets (P<0.0005 and P<0.05, respectively). GSEA indicated that ZNF750 expression was significantly correlated with epithelial differentiation in ESCC. This was confirmed using the datasets from CCLE and the Kyushu University Beppu Hospital by analyzing the levels of small proline rich protein 1A mRNA, an epithelial differentiation-associated gene. In conclusion, the results of the present study suggested that ZNF750 serves a role as a tumor suppressor; potentially via regulating epithelial differentiation and that it may be a promising biomarker of poor outcomes in ESCC.