CHD4/NuRD complex regulates complement gene expression and correlates with CD8 T cell infiltration in human hepatocellular carcinoma

Shao, Simin; Cao, Hua; Wang, Zhongkun; Zhou, Dongmei; Wu, Chaoshen; Wang, Shu; Xia, Dian; Zhang, Daoyong

doi:10.1186/s13148-020-00827-3

Cited by 31 publications

(43 citation statements)

References 28 publications

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“…Numerous researches and clinical studies have con rmed the signi cance of immune in ltration in solid neoplasms. [26]. Wei et al reported that sperm-associated antigen 5 (SPAG5) was a marker of adverse outcome, and its expression was positively associated with the in ltration of neutrophils, CD8+ T cells, B cells , dendritic and macrophages.…”

Section: Discussionmentioning

confidence: 99%

A novel RNA binding protein-associated prognostic model to predict overall survival in hepatocellular carcinoma patients

Liu

Qin

Hai

et al. 2020

Preprint

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Abstract Background Hepatocellular carcinoma (HCC) represents one of the deadliest malignancies worldwide. Despite significant advances in diagnosis and treatment, the mortality rate from HCC persists at a substantial level. This research strives to establish a prognostic model based on the RNA binding proteins (RBPs) that can predict HCC patients’ OS. Methods There was an RNA-seq data set derived from the Cancer Genome Atlas (TCGA) databank which was included in our research as well as a Microarray data set (GSE14520). The differentially expressed RBPs between HCC and normal tissues were investigated in TCGA dataset. Subsequently, the TCGA data set was randomly split into a training and a testing cohort. The prognostic model of the training cohort was developed by applying univariate Cox regression and lasso Cox regression analyses and multivariate Cox regression analysis. In order to evaluate the prognostic value of the model, a comprehensive survival assessment was conducted. Results A total of 133 differentially expressed RBPs were identified. Five RBPs (RPL10L, EZH2, PPARGC1A, ZNF239, IFIT1) were used to construct the model. The model accurately predicted the prognosis of liver cancer patients in both the TCGA cohort and the GSE14520 validation cohort. HCC patients could be assigned into a high-risk group and a low-risk group by this model, and the overall survival of these two groups was significantly different. Furthermore, the risk scores obtained by our model were highly correlated with immune cell infiltration. . Conclusions Five RBPs-related prognostic models were constructed and validated to predict OS reliably in HCC individuals. It helps to identify patients at high risk of mortality with the risk prediction score, which optimizes personalized therapeutic decision-making.

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Section: Discussionmentioning

confidence: 99%

A novel RNA binding protein-associated prognostic model to predict overall survival in hepatocellular carcinoma patients

Liu

Qin

Hai

et al. 2020

Preprint

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“…RNA extraction, reverse transcription, and quantitative real‐time PCR were carried out as previously described [20].…”

Section: Methodsmentioning

confidence: 99%

“…TTCTCCGAACGTGTCACGT. Lentivirus preparation was performed as previously described [20]. The lentivirus was then used to infect BT549 cells to knock down C/EBPβ expression followed by selection using puromycin.…”

Section: Cell Culture and Rnaimentioning

confidence: 99%

“…The shRNAs targeting C/EBPb and the control scrambled sequence were as follows: C/EBPb-sh1, GCCGC CGCCTGCCTTTAAATC; C/EBPb-sh2, GCCCTGAGTA ATCGCTTAAAG; shControl, TTCTCCGAACGTGTCA CGT. Lentivirus preparation was performed as previously described [20]. The lentivirus was then used to infect BT549 cells to knock down C/EBPb expression followed by selection using puromycin.…”

Section: Cell Culture and Rnaimentioning

confidence: 99%

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C/EBPβ regulates the JAK/STAT signaling pathway in triple‐negative breast cancer

et al. 2021

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C/EBPβ is a member of the CCAAT/enhancer-binding protein (C/EBP) family, which consists of a number of b-ZIP transcription factors. Although C/EBPβ has been implicated in the development of certain cancers, including breast cancer, it remains unknown whether dysregulation of C/EBPβ in breast cancer is subtype-specific. Moreover, the underlying mechanisms by which C/EBPβ regulates breast cancer carcinogenesis are not fully understood. Here, we present evidence that C/EBPβ is specifically overexpressed in human TNBC samples, but not in non-TNBC samples. C/EBPβ depletion dramatically suppressed TNBC cell growth, migration, invasion, and colony formation ability. A subsequent mechanistic study revealed that the JAK/STAT signaling pathway was upregulated in C/EBPβ_high TNBC samples compared to C/EBPβ_low TNBC samples. C/EBPβ ChIP-seq and QPCR was performed to demonstrate that C/EBPβ directly binds to and regulates JAK/STAT signaling pathway genes in TNBC. Taken together, our data indicate the oncogenic role of C/EBPβ in human TNBC and reveal a novel mechanism by which C/EBPβ promotes TNBC carcinogenesis.

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“…Chromodomain Helicase DNA-binding protein 4 (Chd4) is a chromatin remodeling enzyme that is part of the Nucleosome Remodeling and Deacetylation (NuRD) complex. The NuRD complex is a transcriptional co-repressor that is known to influence chromatin accessibility and enhancer activity 54 , and it has frequently been tied to oncogenesis 55,56,57 . Recently, Goodman et al 28 studied WT and Chd4-knockout (KO) murine cerebellar cells, establishing a relationship between Chd4 and genome architecture in the mammalian brain.…”

Section: Chd4-knockout Versus Wild Type In Murine Cerebellar Granule mentioning

confidence: 99%

Detecting local changes in chromatin architecture with false discovery control

Koch

Yang

Imakaev

et al. 2020

Preprint

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Hi-C experiments are a powerful means to describe the organization of chromatin interactions genome-wide. By using Hi-C data to identify differentially organized genomic regions, relationships between this organization, gene expression, and cell identity may be established. However, Hi-C data exhibit a unique and challenging spatial structure, as genomic loci can show strong correlations when they are nearby in 3D space within the nucleus or 1D space along the chromosome. Consequently, the development of methods that can accurately detect differences between Hi-C samples while controlling false discoveries has remained difficult. To meet this need, we introduce a spatial modeling approach based on sliding window statistics. Using polymer simulations, we illustrate the improved power and precision of our method to identify differentially interacting genomic regions. We further demonstrate our method’s ability to reveal biologically meaningful changes in chromatin architecture through two data analyses concerning the loss of architectural and chromatin remodeling proteins.

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CHD4/NuRD complex regulates complement gene expression and correlates with CD8 T cell infiltration in human hepatocellular carcinoma

Cited by 31 publications

References 28 publications

A novel RNA binding protein-associated prognostic model to predict overall survival in hepatocellular carcinoma patients

A novel RNA binding protein-associated prognostic model to predict overall survival in hepatocellular carcinoma patients

C/EBPβ regulates the JAK/STAT signaling pathway in triple‐negative breast cancer

Detecting local changes in chromatin architecture with false discovery control

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