NAP1L1 Functions as a Tumor Promoter via Recruiting Hepatoma-Derived Growth Factor/c-Jun Signal in Hepatocellular Carcinoma

Zhang, Yewei; Chen, Qian; Li, Bo; Li, Haiyang; Zhao, Xueke; Xiao, Yanyi; Liu, Shu; Zuo, Shi

doi:10.3389/fcell.2021.659680

Cited by 14 publications

(19 citation statements)

References 34 publications

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“…High MECOM expression is an independent factor, which indicates a poor prognosis in HCC patients. Nucleosome Protein Assembly 1 Like 1 (NAP1L1) is associated with the pathogenesis of many cancers, such as breast cancer, colorectal cancer, nasopharyngeal carcinoma, ovarian cancer, lung cancer, glioma, and hepatocellular carcinoma [19][20][21][22][23][24][25]. An elevated NAP1L1 protein level is a signi cantly unfavorable outcome for HCC patients.…”

Section: Discussionmentioning

confidence: 99%

Identification of a chromatin regulator signature and potential candidate drugs for hepatocellular carcinoma

Mao

Tang

2023

Preprint

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Hepatocellular carcinoma (HCC) is a cancerous tumor that has an unfavorable prognosis. The involvement of chromatin regulators (CRs) in the development of cancer is now supported by a growing body of research. Therefore, we aimed at investigate the function and prognostic importance of CRs in HCC patients. From the prior outstanding research, chromatin regulators (CRs) were obtained. The mRNA expression and clinical data were acquired from the TCGA database. Utilizing Cox regression analysis and least absolute shrinkage and selection operator (LASSO) regression analysis, a risk model for predicting the outcome of HCC was created using the prognostic gene. The Kaplan-Meier analysis was conducted in order to compare the prognosis between high-risk and low-risk groups. We also looked into the differences in drug sensitivity between high-risk and low-risk groups. To estimate prospective small molecule drug therapy, the CMAP dataset was employed. A 13 CRs-based model for predicting the prognosis of HCC patients was effectively built and verified. Furthermore, we discovered that the 13 CRs-based model was a standalone prognostic factor. Functional analysis suggested that the majority of the signaling pathways involved in cancer were enriched in CRs. The immune checkpoint and immune cell infiltration were also associated with the CR-based model. Several medications, including Docetaxel, DMOG, Dasatinib, Axitinib, and Vorinostat, were more sensitive for patients in the high-risk category. Eight small molecule drugs could be beneficial in the treatment of people with HCC. As a result, our research offered novel perspectives into the function of CRs in HCC. We identified a trustworthy prognostic biomarker for the survival of HCC patients.

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Section: Discussionmentioning

confidence: 99%

Identification of a chromatin regulator signature and potential candidate drugs for hepatocellular carcinoma

Mao

Tang

2023

Preprint

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“…In addition, the PI3K / AKT / mTOR signaling pathway was inhibited in PRDM8 overexpression by the regulation of NAP1L1 in HCC, which made an antitumor effect ( Chen Z. et al, 2018 ). The upregulation of NAP1L1 can recruit HDGF / c-Ju n, boosting the HCC progression ( Zhang et al, 2021 ). Other scholars claimed that the proliferation of HCC cells and chemotherapy resistance could be enhanced after the high expression of NAP1L1 ( Le et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

NAP1L1 Functions as a Novel Prognostic Biomarker Associated With Macrophages and Promotes Tumor Progression by Influencing the Wnt/β-Catenin Pathway in Hepatocellular Carcinoma

et al. 2022

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Hepatocellular carcinoma (HCC) is regarded as one of the universal cancers in the world. Therefore, our study is based on clinical, molecular mechanism and immunological perspectives to analyze how NAP1L1 affects the progression of HCC. To begin with, the gene expression datasets and clinical data of GSE14520, GSE76427, ICGC, and TCGA are originated from GEO, ICGC, and TCGA databases. Subsequently, DEG screening was performed on data using R studio, and we finally found that 2,145 overlapping DEGs were screened from four datasets at the end. Then, we used R studio to filter the survival-related genes of the GSE76427 and ICGC datasets, and we screened out 101 survival-related genes. Finally, 33 common genes were screened out from 2,145 overlapping DEGs and 101 survival-related genes. Then, NAP1L1 was screened from 33 common genes using the CytoHubba plug-in in Cytoscape software. Furthermore, ground on GEO, ICGC, and TCGA databases, the survival analysis, clinical feature analysis, univariate/multivariate regression analysis, and multiple GSEA were used to study NAP1L1. The Conclusion claimed that HCC patients with higher expression levels of NAP1L1 had a poorer prognosis than those with lower expression levels. Thus, we believe that NAP1L1 is an independent prognostic factor for HCC. In order to shed light on NAP1L1’s molecular mechanism promoting the progression of HCC closely, the GSEA tool was applied to complete the GSEA of the four datasets. Furthermore, the results confirmed that NAP1L1 could promote HCC progression by regulating the G2/M transition of the cell cycle and Wnt signaling pathway. Western blot and flow cytometry were also performed to understand those mechanisms in this study. The result of Western blot showed that NAP1L1 silencing led to downregulation of CDK1 and β-catenin proteins; the result of flow cytometry showed that cell numbers in the G2 phase were significantly increased when NAP1L1 was silenced. Thus, we claimed that NAP1L1 might promote HCC progression by activating the Wnt signaling pathway and promoting cell cycle G2/M transition. In addition, ground on GSE14520 and GSE76427 datasets, and ICGC and TCGA databases, the correlation between NAP1L1 and immune cells was analyzed in HCC patients. At the same time, the TISIDB online database and the TIMER online database were testified to the association between NAP1L1 and immune cells. Hence, the summary shows that NAP1L1 was connected with a certain amount of immune cells. We can speculate that NAP1L1 may influence macrophages to promote HCC progression through some potential mechanisms.

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“…Similar to NPM1, CHAF1A, and ASF1A, NAP1L1 also binds to transcription factors and functions as a coactivator. Zhang [ 50 ] demonstrated that NAP1L1 interacts with c-Jun and activates the c-Jun/CCND1 axis to promote the tumorigenicity of HCC cells. Furthermore, NAP1L1 is associated with the methylation of gene promoter.…”

Section: Histone Chaperones In Digestive Cancersmentioning

confidence: 99%

“…The clinical significance of NAP1L1 as a cancer promoter in digestive cancers is suggested. Zhang and Le [ 50 , 51 ] reported that NAP1L1 is highly expressed in HCC, indicating an unfavorable overall survival. In CRC, Queiroz [ 141 ] also demonstrated the elevated expression and prognostic significance of NAP1L1.…”

Section: Histone Chaperones In Digestive Cancersmentioning

confidence: 99%

Histone Chaperones and Digestive Cancer: A Review of the Literature

Zhao

Cai

Jiang

et al. 2022

Cancers

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Background: The global burden of digestive cancer is expected to increase. Therefore, crucial for the prognosis of patients with these tumors is to identify early diagnostic markers or novel therapeutic targets. There is accumulating evidence connecting histone chaperones to the pathogenesis of digestive cancer. Histone chaperones are now broadly defined as a class of proteins that bind histones and regulate nucleosome assembly. Recent studies have demonstrated that multiple histone chaperones are aberrantly expressed and have distinct roles in digestive cancers. Objective: The purpose of this review is to present the current evidence regarding the role of histone chaperones in digestive cancer, particularly their mechanism in the development and progression of esophageal, gastric, liver, pancreatic, and colorectal cancers. In addition, the prognostic significance of particular histone chaperones in patients with digestive cancer is discussed. Methods: According to PRISMA guidelines, we searched the PubMed, Embase, and MEDLINE databases to identify studies on histone chaperones and digestive cancer from inception until June 2022. Results: A total of 104 studies involving 21 histone chaperones were retrieved. Conclusions: This review confirms the roles and mechanisms of selected histone chaperones in digestive cancer and suggests their significance as potential prognostic biomarkers and therapeutic targets. However, due to their non-specificity, more research on histone chaperones should be conducted in the future to elucidate novel strategies of histone chaperones for prognosis and treatment of digestive cancer.

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NAP1L1 Functions as a Tumor Promoter via Recruiting Hepatoma-Derived Growth Factor/c-Jun Signal in Hepatocellular Carcinoma

Cited by 14 publications

References 34 publications

Identification of a chromatin regulator signature and potential candidate drugs for hepatocellular carcinoma

Identification of a chromatin regulator signature and potential candidate drugs for hepatocellular carcinoma

NAP1L1 Functions as a Novel Prognostic Biomarker Associated With Macrophages and Promotes Tumor Progression by Influencing the Wnt/β-Catenin Pathway in Hepatocellular Carcinoma

Histone Chaperones and Digestive Cancer: A Review of the Literature

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