Xanthine dehydrogenase downregulation promotes TGFβ signaling and cancer stem cell-related gene expression in hepatocellular carcinoma

Chen, Gl; T, Ye; Hl, Chen; Zy, Zhao; Wq, Tang; Ls, Wang; Jl, Xia

doi:10.1038/oncsis.2017.81

Cited by 30 publications

(35 citation statements)

References 55 publications

(80 reference statements)

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“…These findings suggest that certain geographic regions of tumor were more closely related to certain metastatic sites, while other metastatic sites were yet more divergent from the primary tumor. Distinct validated mutations in this cluster would be considered subclonal and included SF3B1, XDH, LTF, and TMEM2, all of which have been implicated in metastasis and poorer prognosis (19)(20)(21)(22). We also analyzed multiregion sequencing data from 2 cases of breast ACC undergoing transformation to high-grade triple-negative breast cancer previously reported by Fusco et al (23).…”

Section: Resultsmentioning

confidence: 99%

“…Deep sequencing and NMF clustering analysis depicted 1 cluster comprising exclusively metastatic lesions with distinct mutations (SF3B1, XDH, LTF, TMEM2) that may promote metastasis ( Figure 7). SF3B1 mutations are well established in cancer, contributing to alternative splicing and implicated in late metastasis in uveal melanoma (19), while XDH mutations have been shown to promote migration and invasion in hepatocellular carcinoma (20). LTF mutations affect cell motility, while TMEM2 (also known as CEMIP2) mutations appear to confer proinvasive and promigratory potential: both genes are known to be associated with breast cancer metastasis (21,22).…”

Section: Discussionmentioning

confidence: 99%

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Genetic hallmarks of recurrent/metastatic adenoid cystic carcinoma

Ochoa

Jayakumaran

et al. 2019

Journal of Clinical Investigation

145

147

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BACKGROUND. Adenoid cystic carcinoma (ACC) is a rare malignancy arising in salivary glands and other sites, characterized by high rates of relapse and distant spread. Recurrent/metastatic (R/M) ACCs are generally incurable, due to a lack of active systemic therapies. To improve outcomes, deeper understanding of genetic alterations and vulnerabilities in R/M tumors is needed. METHODS. An integrated genomic analysis of 1,045 ACCs (177 primary, 868 R/M) was performed to identify alterations associated with advanced and metastatic tumors. Intratumoral genetic heterogeneity, germline mutations, and therapeutic actionability were assessed.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Genetic hallmarks of recurrent/metastatic adenoid cystic carcinoma

Ochoa

Jayakumaran

et al. 2019

Journal of Clinical Investigation

145

147

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“…Studies have shown that in liver, kidney and breast cancer tissues, the expression level of XDH is signi cantly lower than normal tissues, purine catabolism is severely impaired, and anabolic enzymes are increased [16][17][18][19]. This change gives tumor tissue a selective growth advantage through the rescue pathway of nucleic acid biosynthesis [20,21].…”

Section: Introductionmentioning

confidence: 99%

C1QBP regulates apoptosis of renal cell carcinoma via modulating xanthine dehydrogenase (XDH) mediated ROS generation

Wang¹,

Cui²,

Wang³

et al. 2020

Preprint

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Background Complement component 1 Q subcomponent binding protein (C1QBP) is a multifunctional protein and plays a vital role in the progression and metabolism of cancer. Our previous study has revealed that the low expression of C1QBP in renal cell carcinoma (RCC) and knockdown of C1QBP promotes the adhesion and invasion of RCC cells. However, its functions in the metabolism, oxidative stress and apoptosis of RCC cells have not yet been explored. Methods Metabolomics assay was applied to investigate the role of C1QBP in RCC metabolism. C1QBP knockdown and overexpression cells were established via lentiviral infection and subjected to apoptosis and ROS assay in vitro. RNA stability assay and pre-mRNA detection were applied to characterize the mechanism of C1QBP regulating XDH transcription. In vivo, orthotopic tumor xenografts assay was performed to investigate the role of C1QBP progression. Results Metabolomics investigations revealed that C1QBP dramatically diminished the hypoxanthine content in RCC cells. C1QBP promoted the mRNA and protein expression of hypoxanthine catabolic enzyme xanthine dehydrogenase (XDH). Meanwhile, C1QBP regulated the expression of XDH gene at the pre-transcriptional level by regulating XDH transcriptional stimulators IL-6, TNF-α and IFN-γ. Moreover, the expression of C1QBP and XDH was lower in RCC tumors compared with the para-tumor normal tissues, and their down-regulation was associated with higher levels of Fuhrman grade. In RCC cells, C1QBP significantly increased produces reactive oxygen species (ROS) levels, apoptosis, and the expression of apoptotic proteins cleaved caspase-3 and bax/bcl2 via regulating XDH.Conclusions C1QBP promotes the catabolism of hypoxanthine and elevates the apoptosis of RCC cells by modulating XDH-mediated ROS generation.

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“…During egg development of B. mori the amount of uric acid gradually declines until blastokinesis, after which it increases until egg pigmentation [26]. Remarkably, XHD knockdown has been shown to enhance cell mobility and invasion of HepG2 cells, although no effect on cell proliferation was observed [27]. Furthermore, XDH converts retinoic acid to 9-cis retinal [28], and activity of the enzyme is essential in order for JH to induce bristle formation and cuticle production on the abdominal epidermis during pupal and adult development [29].…”

Section: Discussionmentioning

confidence: 99%

Analysis of molecular mechanism for acceleration of polyembryony using gene functional annotation pipeline in Copidosoma floridanum

et al. 2020

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Background: Polyembryony is defined as the formation of several embryos from a single egg. This phenomenon can occur in humans, armadillo, and some endoparasitoid insects. However, the mechanism underlying polyembryogenesis in animals remains to be elucidated. The polyembryonic parasitoid wasp Copidosoma floridanum oviposits its egg into an egg of the host insect; eventually, over 2000 individuals will arise from one egg. Previously, we reported that polyembryogenesis is enhanced when the juvenile hormone (JH) added to the culture medium in the embryo culture. Hence, in the present study, we performed RNA sequencing (RNA-Seq) analysis to investigate the molecular mechanisms controlling polyembryogenesis of C. floridanum. Functional annotation of genes is not fully available for C.floridanum; however, whole genome assembly has been archived. Hence, we constructed a pipeline for gene functional annotation in C. floridanum and performed molecular network analysis. We analyzed differentially expressed genes between control and JH-treated molura after 48 h of culture, then used the tblastx program to assign whole C. floridanum transcripts to human gene. Results: We obtained 11,117 transcripts in the JH treatment group and identified 217 differentially expressed genes compared with the control group. As a result, 76% of C. floridanum transcripts were assigned to human genes. Gene enrichment analysis revealed genes associated with platelet degranulation, fatty acid biosynthesis, cell morphogenesis in the differentiation and integrin signaling pathways were fluctuated following JH treatment. Furthermore, Cytoscape analysis revealed a molecular interaction that was possibly associated with polyembryogenesis. Conclusions: We have constructed a pipeline for gene functional annotation of C. floridanum, and identified transcripts with high similarity to human genes during early embryo developmental. Additionally, this study reveals new molecular interactions associated with polyembryogenesis; these interactions could indicate the molecular mechanisms underlying polyembryony. Our results highlight the potential utility of molecular interaction analysis in human twins.

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Xanthine dehydrogenase downregulation promotes TGFβ signaling and cancer stem cell-related gene expression in hepatocellular carcinoma

Cited by 30 publications

References 55 publications

Genetic hallmarks of recurrent/metastatic adenoid cystic carcinoma

Genetic hallmarks of recurrent/metastatic adenoid cystic carcinoma

C1QBP regulates apoptosis of renal cell carcinoma via modulating xanthine dehydrogenase (XDH) mediated ROS generation

Analysis of molecular mechanism for acceleration of polyembryony using gene functional annotation pipeline in Copidosoma floridanum

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