The DDX39B/FUT3/TGFβR-I axis promotes tumor metastasis and EMT in colorectal cancer

He, Chengcheng; Li, Aimin; Lai, Qiuhua; Ding, Jian; Yan, Qun; Liu, Side; Li, Qingyuan

doi:10.1038/s41419-020-03360-6

Cited by 29 publications

(16 citation statements)

References 34 publications

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“…38 It is a complicated pathological process that involves multiple steps, including epithelial to mesenchymal transition, in which cancer cells transit between epithelial and mesenchymal states that facilitating cell dissemination. 39 Our results demonstrated that FUT7 siRNA inhibited the migration, invasion, and EMT of bladder cancer cells, while FUT7 cDNA promoted these cell behaviors (Figures 2 and 3). Overall, our study provided novel and valuable insights into FUT7 as a diagnostic biomarker, prognosis predictor, and therapeutic target for BLCA.…”

Section: Discussionmentioning

confidence: 57%

FUT7 Promotes the Epithelial–Mesenchymal Transition and Immune Infiltration in Bladder Urothelial Carcinoma

Liu¹,

Zheng²,

Chen³

et al. 2021

JIR

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Background Bladder urothelial carcinoma (BLCA) is one of the most frequently appearing, lethal and aggressive malignancies of the genitourinary system with growing morbidity and mortality, which affects human health seriously. Protein glycosylation, catalyzed by specific glycosyltransferase, has been found to be abnormal in several diseases, especially cancer. Fucosyltransferase VII (FUT7), one of the fucosyltransferases, was observed abnormally expressed in various cancers, however, the role of FUT7 in BLCA, and the association between its expression and clinical outcomes or immune infiltration remains unclear. Methodology FUT7 expression in BLCA was analyzed in Oncomine database, which was further confirmed with immunohistochemistry and ELISA. The prognostic value of FUT7 for BLCA was evaluated with PrognoScan database, and its genetic alteration was examined in cBioPortal database. The proliferation, migration, invasion and epithelial–mesenchymal transition (EMT) changes of bladder cancer cells after FUT7 siRNA or cDNA transfection were determined by CCK8, colony formation, transwell and Western blot, respectively. The correlation between FUT7 expression and immune infiltration levels was analyzed in TIMER and TISIDB databases, and the methylation level of FUT7 was detected in UALCAN database. Results The results showed that the expression of FUT7 was increased in BLCA, and patients with high FUT7 level were predicted to have lower overall survival and disease-specific survival rates, which were not influenced by FUT7 genetic alterations. Downregulation FUT7 inhibited the proliferation, migration, invasion and EMT of bladder cancer cells, whereas upregulation of FUT7 showed the opposite effects. We found that FUT7 was positively correlated with immune cell infiltration levels (CD8+ T cells, CD4+T cells, macrophage, neutrophil and dendritic cells), and also the expression of gene markers of immune cells. The negative correlation between FUT7 expression and FUT7 methylation level was observed, among which FUT7 expression was positively correlated with the abundance of 28 kinds of tumor-infiltrating lymphocytes (TILs), while FUT7 methylation level was negatively correlated with TILs. Conclusion Altogether, these findings suggested that FUT7 possessed the potential to serve as a detection biomarker or immunotherapeutic target for BLCA.

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Section: Discussionmentioning

confidence: 57%

FUT7 Promotes the Epithelial–Mesenchymal Transition and Immune Infiltration in Bladder Urothelial Carcinoma

Liu¹,

Zheng²,

Chen³

et al. 2021

JIR

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“…As for DDX39B , its functions in HCC progression have not been studied yet. However, recent studies have revealed that increased DDX39B could promote the tumour metastasis of colorectal cancer and enhance chemotherapy resistance in BRCA1-proficient ovarian cancers ( Xu Z. et al, 2020 ; He et al, 2021 ). In our study, we also found that DDX39B was upregulated in HCC tissues and high DDX39B expression was correlated to poor OS and DFS in HCC patients based on the TCGA database.…”

Section: Discussionmentioning

confidence: 99%

Construction and Comprehensive Analysis of a circRNA-miRNA-mRNA Regulatory Network to Reveal the Pathogenesis of Hepatocellular Carcinoma

Liu

Luo

et al. 2022

Front. Mol. Biosci.

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Background: Circular RNAs (circRNAs) have been demonstrated to be closely related to the carcinogenesis of human cancer in recent years. However, the molecular mechanism of circRNAs in the pathogenesis of hepatocellular carcinoma (HCC) has not been fully elucidated. We aimed to identify critical circRNAs and explore their potential regulatory network in HCC.Methods: The robust rank aggregation (RRA) algorithm and weighted gene co-expression network analysis (WGCNA) were conducted to unearth the differentially expressed circRNAs (DEcircRNAs) in HCC. The expression levels of DEcircRNAs were validated by quantitative real-time polymerase chain reaction (qRT-PCR). A circRNA-miRNA-mRNA regulatory network was constructed by computational biology, and protein-protein interaction (PPI) network, functional enrichment analysis, survival analysis, and infiltrating immune cells analysis were performed to uncover the potential regulatory mechanisms of the network.Results: A total of 22 DEcircRNAs were screened out from four microarray datasets (GSE94508, GSE97332, GSE155949, and GSE164803) utilizing the RRA algorithm. Meanwhile, an HCC-related module containing 404 circRNAs was identified by WGCNA analysis. After intersection, only four circRNAs were recognized in both algorithms. Following qRT-PCR validation, three circRNAs (hsa_circRNA_091581, hsa_circRNA_066568, and hsa_circRNA_105031) were chosen for further analysis. As a result, a circRNA-miRNA-mRNA network containing three circRNAs, 17 miRNAs, and 222 mRNAs was established. Seven core genes (ESR1, BUB1, PRC1, LOX, CCT5, YWHAZ, and DDX39B) were determined from the PPI network of 222 mRNAs, and a circRNA-miRNA-hubgene network was also constructed. Functional enrichment analysis suggested that these seven hub genes were closely correlated with several cancer related pathways. Survival analysis revealed that the expression levels of the seven core genes were significantly associated with the prognosis of HCC patients. In addition, we also found that these seven hub genes were remarkably related to the infiltrating levels of immune cells.Conclusion: Our research identified three pivotal HCC-related circRNAs and provided novel insights into the underlying mechanisms of the circRNA-miRNA-mRNA regulatory network in HCC.

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“…For example, fucosyltransferase 3/6 are thought to involve in transforming growth factor-b (TGFb)-mediated pathways regarding cancer cell metastasis and subsequently contributes to the EMT program (131). Recently, an increase in FUT3 regulated by DDX39B catalyzes the aberrant L-fucosylation of TGFbR-I, which enhances the DDX39B-mediated TGFb/SMAD2 signaling pathway and finally facilitates the invasion and metastasis in the colorectal cancer development (132). The mechanisms underlying these discrepant findings, together with the contributions of glycosyltransferases to the metastasis of cervical cancer remain ambiguous, to a certain extent because our comprehension of how glycosylated proteins are regulated by glycosyltransferases remain unclear (129).…”

Section: Discussionmentioning

confidence: 99%

Glycosylation in Cervical Cancer: New Insights and Clinical Implications

Zhang

Ocansey

et al. 2021

Front. Oncol.

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Cervical cancer has become the most frequent female malignancy and presents as a general health challenge in many countries undergoing economic development. Various human papillomaviruses (HPV) types have appeared as one of the most critically identifiable causes of widespread cervical cancers. Conventional cervical cytological inspection has limitations of variable sensitivity according to cervical cytology. Glycobiology has been fundamental in related exploration in various gynecologic and reproductive fields and has contributed to our understanding of cervical cancer. It is associated with altered expression of N-linked glycan as well as abnormal expression of terminal glycan structures. The analytical approaches available to determine serum and tissue glycosylation, as well as potential underlying molecular mechanisms involved in the cellular glycosylation alterations, are monitored. Moreover, cellular glycosylation influences various aspects of cervical cancer biology, ranging from cell surface expressions, cell-cell adhesion, cancer signaling, cancer diagnosis, and management. In general, discoveries in glycan profiling make it technically reproducible and affordable to perform serum glycoproteomic analyses and build on previous work exploring an expanded variety of glycosylation markers in the majority of cervical cancer patients.

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The DDX39B/FUT3/TGFβR-I axis promotes tumor metastasis and EMT in colorectal cancer

Cited by 29 publications

References 34 publications

FUT7 Promotes the Epithelial–Mesenchymal Transition and Immune Infiltration in Bladder Urothelial Carcinoma

FUT7 Promotes the Epithelial–Mesenchymal Transition and Immune Infiltration in Bladder Urothelial Carcinoma

Construction and Comprehensive Analysis of a circRNA-miRNA-mRNA Regulatory Network to Reveal the Pathogenesis of Hepatocellular Carcinoma

Glycosylation in Cervical Cancer: New Insights and Clinical Implications

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