Identification of key genes and important histone modifications in hepatocellular carcinoma

Liu, Yu-Xian; Li, Qian‐Zhong; Cao, Yan-Ni; Zhang, Lu-Qiang

doi:10.1016/j.csbj.2020.09.013

Cited by 23 publications

(11 citation statements)

References 50 publications

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“…Histone H2A variants have previously been demonstrated as a biomarker of tumor progression in several types of human cancers (44). In particular, H2A.Z is overexpressed in multiple malignant tumors, such as breast cancer (45), prostate cancer (46), bladder cancer (47), liver cancer (48,49), as well as malignant melanoma (50,51). Both H2A.Z isoforms are highly expressed in human melanoma and high expression levels correlate with poor prognosis (52).…”

Section: Discussionmentioning

confidence: 99%

H2AFZ: A Novel Prognostic Marker in Canine Melanoma and a Predictive Marker for Resistance to CDK4/6 Inhibitor Treatment

et al. 2021

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Uncontrolled proliferation is a key feature of tumor progression and malignancy. This suggests that cell-cycle related factors could be exploited as cancer biomarkers and that pathways specifically involved in the cell cycle, such as the Rb-E2F pathway, could be targeted as an effective anti-tumor therapy. We investigated 34 formalin-fixed paraffin-embedded (FFPE) tissue samples of canine cutaneous melanocytoma, cutaneous melanoma, and oral melanoma. Corresponding clinical follow-up data were used to determine the prognostic value of the mRNA expression levels of several cell cycle regulated E2F target genes (E2F1, DHFR, CDC6, ATAD2, MCM2, H2AFZ, GINS2, and survivin/BIRC5). Moreover, using four canine melanoma cell lines, we explored the possibility of blocking the Rb-E2F pathway by using a CDK4/6 inhibitor (Palbociclib) as a potential anti-cancer therapy. We investigated the expression levels of the same E2F target gene transcripts before and after treatment to determine the potential utility of these molecules as predictive markers. The E2F target gene H2AFZ was expressed in 91.43% of the primary tumors and H2AFZ expression was significantly higher in cases with unfavorable clinical outcome. Among the other tested genes, survivin/BIRC5 showed as well-promising results as a prognostic marker in canine melanoma. Three of the four tested melanoma cell lines were sensitive to the CDK4/6 inhibitor. The resistant cell line displayed higher expression levels of H2AFZ before treatment compared to the CDK4/6 inhibitor-sensitive cell lines. The present results suggest that CDK4/6 inhibitors could potentially be used as a new anti-cancer treatment for canine melanoma and that H2AFZ could serve as a prognostic and predictive marker for patient selection.

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Section: Discussionmentioning

confidence: 99%

H2AFZ: A Novel Prognostic Marker in Canine Melanoma and a Predictive Marker for Resistance to CDK4/6 Inhibitor Treatment

et al. 2021

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“…Epigenetic modifications have been extensively studied in various human diseases, and their effect on autoimmune diseases has drawn increasing attention. As the major event in epigenetic modification, some studies have shown that H3K27 acetylation plays a role in various cancers, such as increased H3K27ac signals in colon cancer [ 33 ] and hepatocellular carcinoma [ 34 ]. However, to date, the contribution of epigenetic events to the pathogenesis of IBD remains elusive.…”

Section: Discussionmentioning

confidence: 99%

STAT1 epigenetically regulates LCP2 and TNFAIP2 by recruiting EP300 to contribute to the pathogenesis of inflammatory bowel disease

Chen

Zhu

et al. 2021

Clin Epigenet

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Background The aetiology of inflammatory bowel disease (IBD) is related to genetics and epigenetics. Epigenetic regulation of the pathogenesis of IBD has not been well defined. Here, we investigated the role of H3K27ac events in the pathogenesis of IBD. Based on previous ChIP-seq and RNA-seq assays, we studied signal transducer and activator of transcription 1 (STAT1) as a transcription factor (TF) and investigated whether the STAT1–EP300–H3K27ac axis contributes to the development of IBD. We performed ChIP-PCR to investigate the interaction between STAT1 and H3K27ac, and co-IP assays were performed to investigate the crosstalk between STAT1 and EP300. Results Lymphocyte cytosolic protein 2 (LCP2) and TNF-α‐inducible protein 2 (TNFAIP2) are target genes of STAT1. p-STAT1 binds to the enhancer loci of the two genes where H3K27ac is enriched, and EP300 subsequently binds to regulate their expression. In mice with dextran sulfate sodium (DSS)-induced acute colitis, an EP300 inhibitor significantly inhibited colitis. Conclusions p-STAT1 and EP300 promote TNFAIP2 and LCP2 expression through an increase in H3K27ac enrichment on their enhancers and contribute to the pathogenesis of chronic inflammation. Graphic abstract

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“…In eukaryotic cells, posttranscriptional modification of histones and their variants is closely related to gene transcription, and H2A.Z acetylation is known to result in an open chromatin state that promotes downstream gene transcription [ 18 , 19 ]. In addition, Liu et al [ 51 ], using high-throughput computing technology, studied the modification of important histones in HCC and found that the acetylation level of H2A.Z was increased in HCC cell lines, which was related to the highly expressed genes in the HCC cell lines. In our study, RNA-seq and ChIP-seq analyses of H2A.Z showed it to mainly promote the transcription of downstream genes in HCC, thereby suggesting the acetylation levels of H2A.Z in HCC to possibly be increased.…”

Section: Discussionmentioning

confidence: 99%

H2A.Z acetylation by lincZNF337-AS1 via KAT5 implicated in the transcriptional misregulation in cancer signaling pathway in hepatocellular carcinoma

et al. 2021

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In eukaryotes, histones and their variants are essential for chromatin structure and function; both play important roles in the regulation of gene transcription, as well as the development of tumors. We aimed to explore the genomics data of hepatocellular carcinoma (HCC), combined with literature analysis, in terms of the histone variant H2A.Z. Cell phenotype assay confirmed the effect of H2A.Z on the proliferation, metastasis, apoptosis, and cell cycle of HCC cells. H2A.Z was shown to function via the tumor dysregulation signaling pathway, with BCL6 as its interacting protein. In addition, the acetylation level of H2A.Z was higher in HCC and was related to tumor formation. We found the acetylation of H2A.Z to be related to and regulated by lincZNF337-AS1. LincZNF337-AS1 was found to bind to H2A.Z and KAT5 at different sites, promoting the acetylation of H2A.Z through KAT5. We concluded that, in HCC, H2A.Z is an oncogene, whose acetylation promotes the transcription of downstream genes, and is regulated by lincZNF331-AS1.

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Identification of key genes and important histone modifications in hepatocellular carcinoma

Abstract: Graphical abstract

Cited by 23 publications

References 50 publications

H2AFZ: A Novel Prognostic Marker in Canine Melanoma and a Predictive Marker for Resistance to CDK4/6 Inhibitor Treatment

H2AFZ: A Novel Prognostic Marker in Canine Melanoma and a Predictive Marker for Resistance to CDK4/6 Inhibitor Treatment

STAT1 epigenetically regulates LCP2 and TNFAIP2 by recruiting EP300 to contribute to the pathogenesis of inflammatory bowel disease

H2A.Z acetylation by lincZNF337-AS1 via KAT5 implicated in the transcriptional misregulation in cancer signaling pathway in hepatocellular carcinoma

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