FASEB JOURNAL
·
2026
·Vol. 40
·期 6
·e71634
·
IF 4.3
Wenyu Gao,Hao Chen,Fangyu Lin,Jialin Liu,Tingxuan Huang,Han Wang,Xiaojiao Weng,Xinli Wang,Xiaoyan Lin,Tao Jiang
Gastric cancer (GC) is a leading cause of cancer‐related deaths and has high recurrence rate. Although fibronectin domain‐containing protein 1 (FNDC1) is implicated in GC progression, its molecular mechanisms remain unclear. Multi‐omics analyses (TCGA, GEO datasets) were used to assess FNDC1 expression and clinical correlation. In vitro (cell proliferation, invasion, EMT markers) and in vivo (xenograft) experiments, combined with molecular assays (Co‐IP, WB, ChIP), explored FNDC1's function and mechanism. FNDC1 was significantly upregulated in GC, correlating with advanced clinicopathological features and poor prognosis. Knockdown of FNDC1 suppressed GC cell proliferation, invasion, and metastasis by inhibiting EMT and Wnt/β‐catenin signaling. Mechanistically, FNDC1 competitively bound the WD5 domain (residues 224–254) of Gβ2, disrupting Gβγ–Dvl1 interaction. This prevented Dvl1 degradation, promoted Axin1 ubiquitination, and destabilized the β‐catenin–destruction complex (GSK3 β–APC–Axin1), leading to β‐catenin accumulation and Wnt pathway activation. FNDC1 drives GC malignancy by targeting the Gβ2–Dvl1 axis to activate Wnt/β‐catenin signaling, suggesting FNDC1 as a novel prognostic biomarker and therapeutic target. FNDC1 competitively binds Gβ2 to suppress the β‐catenin–destruction complex and promote the malignant behavior of gastric cancer (GC) by the following mechanism: elevated FNDC1 competes with Dvl for binding to Gβ2, thereby reducing Dvl–Gβ2 interaction; this reduction inhibits Dvl degradation in the cytoplasm; increased Dvl recruits Axin1, thereby disrupting the β‐catenin–destruction complex (GSK3β–APC–Axin) and blocking ubiquitination and degradation of β‐catenin; accumulated β‐catenin in the cytoplasm translocates to the nucleus, where it activates Wnt target genes and promotes epithelial–mesenchymal transition (EMT) in GC cells.
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产品关联
DOI
PubMed
高影响因子
Frontiers in Oncology
·
2020
·
IF 4.848
Jiang Tao,Gao Wenyu,Lin Shengjie,Chen Hao,Du Bin,Liu Qing,Lin Xiaoyan,Chen Qiang
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 in vivo and in vitro. 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 in vivo and in vitro 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.
研究领域:
肿瘤学
·
分子生物学
·
癌症研究
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DOI
PubMed
高影响因子
Experimental and Therapeutic Medicine
·
2021
·Vol. 22
·期 1
·1-8
·
IF 2.447
Peng Yi,Xiongfeng Xu,Jiawei Yao,Bo Qiu
Genetics and epigenetics are important subjects in the field of osteoarthritis (OA) research. DNA methylation may affect gene transcription, but the specific mechanisms have remained to be fully elucidated. In the present study, the ChAMP methylation analysis package was used to identify differentially methylated genes (DMGs) from the dataset GSE63695 from the Gene Expression Omnibus (GEO) database. The distribution of differentially methylated sites (DMS) and the total array sites across the genome were analyzed by enrichment analysis. Subsequently, two mRNA expression profiling datasets, GSE114007 and GSE113825, were obtained from the GEO database and common differentially expressed genes (DEGs) were identified using the Limma package. Key genes were screened by analyzing the distribution of DMS across the genome consisting of DEGs and DMGs. A total of 1,662 and 1,986 DEGs were identified between OA and normal human cartilage from the GSE113825 and GSE114007 dataset, respectively. A further screening revealed 292 genes with common differences between the two datasets. A total of 574 DMS containing 394 DMGs were observed between OA and normal cartilage. Integrative analysis revealed a corresponding subset of 15 genes. Of these, 6 genes were verified by reverse transcription‑quantitative PCR, confirming that the mRNA expression of 5 genes (MAP1B, FNDC1, ANLN, SCNN1A and STC2) in OA cartilage was consistent with the mRNA expression from the analysis of the datasets. Upon treatment with the DNA methylation inhibitor 5‑aza‑2'‑deoxycytidine, the mRNA levels of FNDC1 and SCNN1A were decreased, and no significant alteration in the mRNA levels of MAP1B, ANLN, KCNN4 and STC2 was observed. The incidence of differential methylation varied in subregions of the genome and the effects on transcription were associated with the distribution of DEGs across the genome. The regulation of this appears more complex than initially postulated. Combining the data on epigenetic differences of OA with the genome or transcriptome data for analysis may improve the understanding of the pathophysiological processes of OA. FNDC1 and SCNN1A may potentially be valuable biomarkers for OA.
研究领域:
遗传学
·
表观遗传学
·
骨科
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
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