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FNDC1通过Wnt/β-连环蛋白信号通路促进胃癌侵袭,并与腹膜转移及预后相关。

FNDC1 Promotes the Invasiveness of Gastric Cancer Wnt/β-Catenin Signaling Pathway and Correlates With Peritoneal Metastasis and Prognosis.

作者信息

Jiang Tao, Gao Wenyu, Lin Shengjie, Chen Hao, Du Bin, Liu Qing, Lin Xiaoyan, Chen Qiang

机构信息

Department of Medical Oncology, Fujian Medical University Union Hospital, Fuzhou, China.

Department of Digestive, Fujian Medical University Union Hospital, Fuzhou, China.

出版信息

Front Oncol. 2020 Dec 17;10:590492. doi: 10.3389/fonc.2020.590492. eCollection 2020.

Abstract

BACKGROUND

Gastric cancer (GC) has a high morbidity and mortality rate, with peritoneal metastasis (PM) identified as the main site of metastasis. Our previous study found that FNDC1 has a higher frequency of mutations in patients with PM by high-throughput sequencing assay, suggesting that it may be associated with GC invasion and PM, however the specific mechanism remains unclear.

METHODS

First, the correlation between FNDC1 and PM and prognosis of GC was clarified by bioinformatics and clinicopathological analysis. Next, the effect of FNDC1 expression on the invasion and metastasis ability of GC was investigated and . Finally, the signaling pathways involved in the regulation of FNDC1 were explored.

RESULTS

FNDC1 was highly expressed in GC and was associated with PM and poor prognosis. FNDC1 was also associated with epithelial-mesenchymal transition (EMT) in GC cells. Through and experiments, it was clarified that knockdown of FNDC1 could inhibit the proliferation, invasion, and migration of GC cells. In addition, it was elucidated that FNDC1 promotes EMT through the Wnt/β-catenin signaling pathway.

CONCLUSION

FNDC1 may be associated with the invasion of GC and PM after surgery. FNDC1 was highly expressed in GC tissues and cell lines, while significantly associated with poor DFS and OS in GC patients. Both univariate and multivariate analyses suggested that the expression of FNDC1 was an independent factor for GC. Knockdown of FNDC1 also significantly inhibited the proliferation, migration, and activity of GC cells. FNDC1 may promote EMT in GC cells through the regulation of Wnt/β-catenin signaling pathway. FNDC1 has the potential to be used as a predictor of PM and may also be studied in depth as a therapeutic target for GC, which has potential clinical utility and is worthy of further validation.

摘要

背景

胃癌(GC)的发病率和死亡率很高,腹膜转移(PM)是主要的转移部位。我们之前的研究通过高通量测序分析发现,FNDC1在PM患者中的突变频率较高,提示其可能与GC侵袭和PM相关,但其具体机制仍不清楚。

方法

首先,通过生物信息学和临床病理分析阐明FNDC1与GC的PM及预后之间的相关性。其次,研究FNDC1表达对GC侵袭和转移能力的影响。最后,探索参与FNDC1调控的信号通路。

结果

FNDC1在GC中高表达,与PM及不良预后相关。FNDC1还与GC细胞的上皮-间质转化(EMT)有关。通过实验明确,敲低FNDC1可抑制GC细胞的增殖、侵袭和迁移。此外,阐明了FNDC1通过Wnt/β-连环蛋白信号通路促进EMT。

结论

FNDC1可能与GC术后侵袭及PM相关。FNDC1在GC组织和细胞系中高表达,与GC患者较差的无病生存期(DFS)和总生存期(OS)显著相关。单因素和多因素分析均表明,FNDC1的表达是GC的独立因素。敲低FNDC1也显著抑制了GC细胞的增殖、迁移和活性。FNDC1可能通过调控Wnt/β-连环蛋白信号通路促进GC细胞的EMT。FNDC1有潜力作为PM的预测指标,也可能作为GC的治疗靶点进行深入研究,具有潜在的临床应用价值,值得进一步验证。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/319b/7773909/a79b2698de6c/fonc-10-590492-g001.jpg

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