The role of UXT in tumors and prospects for its application in hepatocellular carcinoma

Wang, Zhengwang; Mo, Shaojian; Han, Pengzhe; Liu, Lu; Liu, Ziang; Fu, Xinping; Tian, Yanzhang

doi:10.2217/fon-2022-0582

Cited by 2 publications

(4 citation statements)

References 91 publications

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“…We detected high expression levels of UXT‐V1 in the colonic crypts of patients with UC, particularly in the colonic epithelium. On a subcellular level, UXT‐V1 was mainly present in the cytoplasm, which is consistent with previous findings 19,22,43 . We have also shown for the first time that UXT‐V1 promotes colonic goblet cell differentiation by inhibiting the nuclear translocation of ZONAB by sequestering it in the cytoplasm.…”

Section: Discussionsupporting

confidence: 92%

“…The ubiquitous expressed transcript (UXT), a member of the prefoldin‐like protein family, has gained increasing attention in the context of health and disease 18,19 . UXT contains two mRNA splicing variants that generate two UXT isoforms, UXT‐V1 and UXT‐V2, respectively.…”

Section: Introductionmentioning

confidence: 99%

“…The ubiquitous expressed transcript (UXT), a member of the prefoldin-like protein family, has gained increasing attention in the context of health and disease. 18,19 UXT contains two mRNA splicing variants that generate two UXT isoforms, UXT-V1 and UXT-V2, respectively. Previous studies have demonstrated that UXT is highly expressed in colorectal tumor tissues and is involved in cell proliferation or differentiation.…”

Section: Introductionmentioning

confidence: 99%

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Regulation of epithelial cell differentiation by the Ubiquitous expressed transcript isoform 1 in ulcerative colitis

Peng,

Zeng,

et al. 2023

J of Gastro and Hepatol

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Background and AimMucosal healing has emerged as a desirable treatment goal for patients with ulcerative colitis (UC). Healing of mucosal wounds involves epithelial cell proliferation and differentiation, and Y‐box transcription factor ZONAB has recently been identified as the key modulator of intestinal epithelial restitution.MethodsWe studied the characteristics of UXT‐V1 expression in UC patients using immunohistochemistry and qPCR. The functional role of UXT‐V1 in the colonic epithelium was investigated using lentivirus‐mediated shRNA in vitro and ex vivo. Through endogenous Co‐immunoprecipitation and LC–MS/MS, we identified ZONAB as a UXT‐V1‐interactive protein.ResultsHerein, we report that UXT‐V1 promotes differentiation of intestinal epithelial cells by regulating the nuclear translocation of ZONAB. UXT‐V1 was upregulated in the intestinal epithelia of UC patients compared with that of healthy controls. Knocking down UXT‐V1 in NCM‐460 cells led to the enrichment of pathways associated with proliferation and differentiation. Furthermore, the absence of UXT‐V1 in cultured intestinal epithelial cells and colonic organoids inhibited differentiation to the goblet cell phenotype. Mechanistically, the loss of UXT‐V1 in the intestinal epithelial cells allowed nuclear translocation of ZONAB, wherein it regulated the transcription of differentiation‐related genes, including AML1 and KLF4.ConclusionTaken together, our study reveals a potential role of UXT‐V1 in regulating epithelial cell differentiation, proving a molecular basis for mucosal healing in UC.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Regulation of epithelial cell differentiation by the Ubiquitous expressed transcript isoform 1 in ulcerative colitis

Peng,

Zeng,

et al. 2023

J of Gastro and Hepatol

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“…Gene expression technology has been widely employed in previous studies to research and diagnose diseases, including using high-throughput sequencing datasets to explore genes associated with specific diseases. 11 The (Gene Expression Omnibus) GEO database provides a wealth of gene expression data, allowing researchers better to understand various biological processes. 12 For example, by analyzing these data, researchers could identify the characteristic genes related to specific diseases, their relationships with each other, and their roles in developing the diseases.…”

Section: Introductionmentioning

confidence: 99%

Unraveling the copper-death connection: Decoding COVID-19‘s immune landscape through advanced bioinformatics and machine learning approaches

Wang,

Su,

Zhang

et al. 2024

Human Vaccines & Immunotherapeutics

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This study aims to analyze Coronavirus Disease 2019 (COVID-19)-associated copper-death genes using the Gene Expression Omnibus (GEO) dataset and machine learning, exploring their immune microenvironment correlation and underlying mechanisms. Utilizing GEO, we analyzed the GSE217948 dataset with control samples. Differential expression analysis identified 16 differentially expressed copper-death genes, and Cell type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT) quantified immune cell infiltration. Gene classification yielded two copper-death clusters, with Weighted Gene Co-expression Network Analysis (WGCNA) identifying key module genes. Machine learning models (random forest, Support Vector Machine (SVM), Generalized Linear Model (GLM), eXtreme Gradient Boosting (XGBoost)) selected 6 feature genes validated by the GSE213313 dataset. Ferredoxin 1 (FDX1) emerged as the top gene, corroborated by Area Under the Curve (AUC) analysis. Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA) revealed enriched pathways in T cell receptor, natural killer cytotoxicity, and Peroxisome Proliferator-Activated Receptor (PPAR). We uncovered differentially expressed copper-death genes and immune infiltration differences, notably CD8 T cells and M0 macrophages. Clustering identified modules with potential implications for COVID-19. Machine learning models effectively predicted COVID-19 risk, with FDX1‘s pivotal role validated. FDX1‘s high expression was associated with immune pathways, suggesting its role in COVID-19 pathogenesis. This comprehensive approach elucidated COVID-19-related copper-death genes, their immune context, and risk prediction potential. FDX1‘s connection to immune pathways offers insights into COVID-19 mechanisms and therapy.

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The role of UXT in tumors and prospects for its application in hepatocellular carcinoma

Cited by 2 publications

References 91 publications

Regulation of epithelial cell differentiation by the Ubiquitous expressed transcript isoform 1 in ulcerative colitis

Regulation of epithelial cell differentiation by the Ubiquitous expressed transcript isoform 1 in ulcerative colitis

Unraveling the copper-death connection: Decoding COVID-19‘s immune landscape through advanced bioinformatics and machine learning approaches

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