The expression and prognostic value of REXO4 in hepatocellular carcinoma

Chen, Wei-Peng; Gao, Cheng; Shen, Jianbo; Yao, Lan-Qing; Liang, Xiaoliang; Chen, Zhong

doi:10.21037/jgo-21-98

Cited by 4 publications

(3 citation statements)

References 26 publications

(37 reference statements)

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“…Among the lipolysis regulators uncovered in our screen, we found an enrichment for JUN/SMAD family members, which are growth-related proteins that have been linked to lipolytic suppression in adipocytes through lipase gene networks ( 8 , 9 , 42 ). Together with identifying several transcription factors that have been linked to adiposity or metabolic disease in other tissues [KLF2 ( 43 ), KLF7 ( 44 ), REXO4 ( 45 ), and TSC22D1 ( 46 )], these findings validate the utility of our human adipocyte screening platform as a resource of transcriptional regulators of adipocyte lipid mobilization. In this vein, we use protein network mapping to uncover a previously unknown role for histone chaperone proteins and mRNA elongation/splicing factors in regulating adipocyte lipolysis.…”

Section: Discussionsupporting

confidence: 58%

Transcriptional determinants of lipid mobilization in human adipocytes

Ludzki,

Hansen,

Zareifi

et al. 2024

Sci. Adv.

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Defects in adipocyte lipolysis drive multiple aspects of cardiometabolic disease, but the transcriptional framework controlling this process has not been established. To address this, we performed a targeted perturbation screen in primary human adipocytes. Our analyses identified 37 transcriptional regulators of lipid mobilization, which we classified as (i) transcription factors, (ii) histone chaperones, and (iii) mRNA processing proteins. On the basis of its strong relationship with multiple readouts of lipolysis in patient samples, we performed mechanistic studies on one hit, ZNF189 , which encodes the zinc finger protein 189. Using mass spectrometry and chromatin profiling techniques, we show that ZNF189 interacts with the tripartite motif family member TRIM28 and represses the transcription of an adipocyte-specific isoform of phosphodiesterase 1B (PDE1B2). The regulation of lipid mobilization by ZNF189 requires PDE1B2, and the overexpression of PDE1B2 is sufficient to attenuate hormone-stimulated lipolysis. Thus, our work identifies the ZNF189-PDE1B2 axis as a determinant of human adipocyte lipolysis and highlights a link between chromatin architecture and lipid mobilization.

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Section: Discussionsupporting

confidence: 58%

Transcriptional determinants of lipid mobilization in human adipocytes

Ludzki,

Hansen,

Zareifi

et al. 2024

Sci. Adv.

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“…Unlike KDM5B , REXO4 is much less well-investigated in cancer biology. Current literature illustrates overexpression in hepatocellular carcinoma that is associated with tumor progression and immune infiltration [ 47 , 48 ]. Further investigations are needed to unravel the role of KDM5B and REXO4 loss in high-risk UM.…”

Section: Discussionmentioning

confidence: 99%

FOXD1 Is a Transcription Factor Important for Uveal Melanocyte Development and Associated with High-Risk Uveal Melanoma

Bosch

Nguyen

Brands

et al. 2022

Cancers

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Uveal melanoma (UM) is a deadly ocular malignancy, originating from uveal melanocytes. Although much is known regarding prognostication in UM, the exact mechanism of metastasis is mostly unknown. Metastatic tumor cells are known to express a more stem-like RNA profile which is seen often in cell-specific embryonic development to induce tumor progression. Here, we identified novel transcription regulators by reanalyzing publicly available single cell RNA sequencing experiments. We identified five transcription regulators of interest: ELL2, KDM5B, REXO4, RBFOX2 and FOXD1. Our most significant finding is FOXD1, as this gene is nearly exclusively expressed in high-risk UM and its expression is associated with a poor prognosis. Even within the BAP1-mutated UM, the expression of FOXD1 is correlated with poor survival. FOXD1 is a novel factor which could potentially be involved in the metastatic capacity of high-risk UM. Elucidating the function of FOXD1 in UM could provide insight into the malignant transformation of uveal melanocytes, especially in high-risk UM.

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“…Elevated REXO4 expression is linked to unfavorable outcomes in HCC patients and may be connected to immune infiltration in liver cancer. A comprehensive understanding of the role of REXO4 could pave the way for targeted drug therapies and further exploration of its mechanisms in liver cancer carcinogenesis ( 9 ). In addition, PTER protein is significantly up-regulated in HCC tumors, and its high expression is associated with aggressive clinicopathological features, including advanced tumor staging, vascular invasion, recurrence, and shortened OS and disease-free survival (DFS) time.…”

Section: Introductionmentioning

confidence: 99%

Identification of potential prognostic biomarkers among gene models for coiled-coil domain-containing family members in hepatocellular carcinoma elucidates their influence on the hypoxia pathway and immune microenvironment

Li,

Zhang,

Liu

et al. 2023

J Gastrointest Oncol

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Background The family of coiled-coil domain-containing (CCDC) proteins participates in a wide range of physiological functions and plays a pivotal role in governing the invasion and metastasis of malignant tumor cells. Nonetheless, the precise mechanism governing the interaction among the immune microenvironment, hypoxia pathway, and proliferation in hepatocellular carcinoma (HCC) remains elusive. In this study, our objective was to identify the prognostic significance of CCDC family genes in HCC. Methods We conducted an analysis of RNA-seq data from HCC patients sourced from The Cancer Genome Atlas (TCGA) database. Our analysis involved comparing the expression profiles of 168 CCDC family genes between tumor and normal tissues to identify differentially expressed genes (DEGs). The prognostic value of these genes was verified using overall survival (OS) data from TCGA-LIHC patients, employing Univariate and multivariate Cox proportional hazards regression models and Kaplan-Meier plots. Subsequently, we constructed a prognostic signature known as the CCDC score and validated it using additional datasets (ICGC-LIRI-JP and GSE14520). Additionally, we performed functional enrichment analysis and conducted an assessment of the tumor immune microenvironment (TIME). Results We identified 34 DEGs of the CCDC family. Among them, six DEGs ( CCDC6/22/51/59/132/134 ) were upregulated and associated with poor prognosis. Higher CCDC score was an independent predictor of poor OS in TCGA-HCC patients (P<0.001, HR =2.37), which was validated in the ICGC-LIRI-JP (P=0.021, HR =2.15) and GSE14520 (P=0.002, HR =2.23) datasets. Functional enrichment analysis showed that hypoxia pathway genes were enriched in the high CCDC score group. Furthermore, immune microenvironment analysis demonstrated that high CCDC score was associated with a suppressed TIME caused by the extrinsic immune escape. Conclusions The CCDC score, derived from six CCDC genes, exhibits remarkable expression levels in liver cancer and holds promise as an independent prognostic indicator. Our bioinformatics analysis revealed a high CCDC score is strongly associated with activation of the hypoxia pathway and an immunosuppressive tumor microenvironment in HCC. This profound finding may serve as a cornerstone for innovative targeted drug therapies and pave the way for further investigations into the underlying mechanisms of CCDC-related carcinogenesis in liver cancer.

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The expression and prognostic value of REXO4 in hepatocellular carcinoma

Cited by 4 publications

References 26 publications

Transcriptional determinants of lipid mobilization in human adipocytes

Transcriptional determinants of lipid mobilization in human adipocytes

FOXD1 Is a Transcription Factor Important for Uveal Melanocyte Development and Associated with High-Risk Uveal Melanoma

Identification of potential prognostic biomarkers among gene models for coiled-coil domain-containing family members in hepatocellular carcinoma elucidates their influence on the hypoxia pathway and immune microenvironment

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