Identification of TAF1, HNF4A, and CALM2 as potential therapeutic target genes for liver fibrosis

Ji, Dong; Chen, Guofeng; Wang, Jincheng; Cao, Lihua; Lu, Fengmin; Mu, Xiaoxin; Zhang, Xiaoyu; Lu, Xiao‐Jie

doi:10.1002/jcp.27579

Cited by 27 publications

(21 citation statements)

References 40 publications

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“…HNF4a belongs to the transcription factor of nuclear hormone receptor superfamily 2A, which is mainly found in liver, kidney, and intestinal tissues [35][36][37][38]. In lung tissue, the content of HNF4a is low and its positive expression can even be used as a useful marker for difficult diagnosis in small biopsy samples [39].…”

Section: Discussionmentioning

confidence: 99%

Research on the circadian clock gene HNF4a in different malignant tumors

Qiu¹,

Zhang²,

Fang³

et al. 2021

Int. J. Med. Sci.

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Background: The circadian rhythm is produced by multiple feedback loops formed by the core clock genes after transcription and translation, thus regulating various metabolic and physiological functions of the human body. We have shown previously that the abnormal expression of 14 clock genes is related closely to the occurrence and development of different malignant tumors, and these genes may play an anti-cancer or pro-cancer role in different tumors. HNF4a has many typical properties of clock proteins involved in the clock gene negative feedback loop regulation process. We need to explore the function of HNF4a as a circadian clock gene in malignant tumors further. Methods: We used The Cancer Genome Atlas (TCGA) database to download the clinicopathological information of twenty malignant tumors and the corresponding RNA-seq data. The HNF4a RNA-seq data standardized by R language and clinical information were integrated to reveal the relationship between HNF4a and prognosis of patients. Results: Analysis of TCGA data showed that the prognosis of HNF4a was significantly different in BLCA, KIRC, LUSC, and READ. High HNF4a expression is correlated with good prognosis in BLCA, KIRC, and READ but poor prognosis in LUSC. However, HNF4a was associated with the stages, T stages, and lymph node status only in BLCA. Conclusions: HNF4a plays different roles in different malignancies, and the abnormal expression of HNF4a has a great correlation with the biological characteristics of BLCA. The low expression of HNF4a could be a reference index for the metastasis, recurrence, and prognosis of BLCA.

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Section: Discussionmentioning

confidence: 99%

Research on the circadian clock gene HNF4a in different malignant tumors

Qiu¹,

Zhang²,

Fang³

et al. 2021

Int. J. Med. Sci.

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“…In this study, we screened six hub genes that may be associated with both HCV infection and alcohol consumption, including TAF1, SAT1, PLCB2, FGD1, ARHGAP4, and ARHGEF9. Among them, studies have shown that TAF1 might be a potential therapeutic target gene for liver fibrosis (Ji et al, ), implying its key role in the development of HCC and potential role as a biomarker. SAT1 is a key regulator of AKT/β‐catenin signaling pathways.…”

Section: Discussionmentioning

confidence: 99%

Identification of TAF1, SAT1, and ARHGEF9 as DNA methylation biomarkers for hepatocellular carcinoma

Cai

Xie

Zhou

et al. 2019

Journal Cellular Physiology

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Hepatocellular carcinoma (HCC) is a major cause of cancer-related deaths worldwide.More than 90% of primary HCC is HCC. Hepatitis C virus (HCV) infection and alcohol consumption have been widely accepted as two major risk factors for developing HCC. Herein, we aimed to identify DNA methylation genes related to both HCV infection and alcohol consumption. In this study, we identified methylation genes that were associated with the risk of HCV infection and alcohol consumption, respectively, by a large-scale bioinformatic analysis. Through PPI network analysis, we revealed the associations between the two types of genes and found six hub genes-TAF1, SAT1, Phospholipase C-beta 2, FGD1, ARHGAP4, and ARHGEF9-that may be associated with both HCV infection and alcohol consumption. Gene Ontology enrichment analysis was used to analyze the function which these genes in the network enriched. Among them, TAF1, SAT1, and ARHGEF9 were methylated genes that have been found to be related to tumor progression in HCC patients. Through independent data sets, we verified the methylation pattern of these six genes in HCC samples that had both HCV infection and alcohol consumption risks. Furthermore, we found that three of the six methylated genes were also associated with the prognosis of HCC patients. To summarize, we identified six hub genes that were associated with both HCV infection and alcohol consumption in the progress of HCC. The six methylation genes that might play an important role in both HCV infection and alcohol consumption would be potential therapy targets for HCC. K E Y W O R D S alcohol consumption, hepatitis C virus infection, hepatocellular carcinoma, methylation

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“…The proteins in STAT3 signaling pathway played important roles in HCV infection or HCC (Ji et al, ; Kao et al, ; Qadri et al, ). HCV infection could lead to increasing of HNF1A and HNF4A proteins, which caused upregulation of ABCC2 (Qadri et al, ).…”

Section: Discussionmentioning

confidence: 99%

STAT3 signaling pathway plays importantly genetic and functional roles in HCV infection

Song

Yang

Shen

et al. 2019

Molec Gen & Gen Med

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Background Hepatitis C virus (HCV) infection is an extensive health problem, which leads to serious liver diseases. Host genetic polymorphisms were associated with HCV infection, progression, and treatment effect of patients. Signal transducers and activators of transcription 3 (STAT3) signaling pathway was important to HCV infection, but no genetic association was studied between STAT3 signaling pathway and HCV infection. Methods To investigate the genetic and functional roles of the STAT3 signaling pathway, we collected 394 HCV patients and 395 normal controls to genotype 25 signal nucleotide polymorphisms (SNPs) of six genes (Interleukin 6 [IL6, OMIM 147620], Interleukin 6 receptor [IL6R, OMIM 147880], Hepatocyte nuclear factor 1 alpha [HNF1A, OMIM 142410], Hepatocyte nuclear factor 4 alpha [HNF4A, OMIM 600281], STAT3 [OMIM 102582], and ATP binding cassette subfamily C member 2 [ABCC2, OMIM 601107]). Then expression level of these genes were analyzed in HCV infected cells with or without IL6 transfection. Results Our results identified that the SNPs in STAT3 signaling pathway were associated with HCV infection or biochemical features of Yunnan HCV patients. Genotype AA of rs4075015 (IL6R) and GG of rs3212172 (HNF4A) increased the risk of HCV infection (p = 0.024 and 0.029), but the genotype AA of rs7553796 (IL6R) played a protective role in HCV infection (p = 0.0008). High‐density lipoprotein cholesterol (HDL‐C) and Glutamyl transpeptidase (GGT) level were associated with genotypes of rs4845617 (IL6R, p = 0.045) and rs1053023 (STAT3, p = 0.034), respectively. Cell assays suggested that IL6 transfection could suppress HCV proliferation. RNA and protein levels of the IL6R, HNF1A, STAT3, and ABCC2 genes significantly increased after HCV infection. Conclusion We identified STAT3 signaling pathway influenced HCV infection and biochemical characteristics of HCV patients through genetic and functional aspects.

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Identification of TAF1, HNF4A, and CALM2 as potential therapeutic target genes for liver fibrosis

Cited by 27 publications

References 40 publications

Research on the circadian clock gene HNF4a in different malignant tumors

Research on the circadian clock gene HNF4a in different malignant tumors

Identification of TAF1, SAT1, and ARHGEF9 as DNA methylation biomarkers for hepatocellular carcinoma

STAT3 signaling pathway plays importantly genetic and functional roles in HCV infection

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