CHAF1A interacts with TCF4 to promote gastric carcinogenesis via upregulation of c-MYC and CCND1 expression

Zheng, Lixin; Liang, Xiao; Li, Shuyan; Li, Tongyu; Shang, Wenjing; Ma, Lin; Jia, Xiaxia; Shao, Wei; Sun, Pengpeng; Chen, Chunyan; Jia, Jihui

doi:10.1016/j.ebiom.2018.11.009

Cited by 32 publications

(41 citation statements)

References 46 publications

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“…Chromatin assembly factor 1 subunit A (CHAF1A) is a pro-oncogene that plays a role in a variety of tumors, such as colon cancer (Wu et al, 2014), glioblastoma (Peng et al, 2016), ovarian cancer (Xia et al, 2017) and gastric cancer (Zheng et al, 2018). In addition, studies showed that the expression of CHAF1A was increased in cervical cancer and was positively correlated with tumor malignancy (Luo et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

MiR-1179 is downregulated in cervical cancer and its overexpression suppresses cancer cells invasion by targeting CHAF1A/ZEB1

Zhong

Sang

et al. 2021

Acta Biochim Pol

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The anticancer effect of miR-1179 has been extensively studied in many tumors. The mechanism of miR-1179 action in cervical cancer, however, remains largely unknown. In the present study, miR-1179 was downregulated in both cervical cancer cell lines and cancer tissues. In addition, miR-1179 mimic suppressed cancer cells invasion and epithelial-mesenchymal transition (EMT) in cervical cancer SiHa and Caski cells. We found that chromatin assembly factor 1 subunit A (CHAF1A) might be a direct target of miR-1179 and could be regulated by miR-1179. Furthermore, CHAF1A shRNA suppressed the cervical cancer cells invasion and the expression of EMT-promoted proteins. Reversely, CHAF1A overexpression not only promoted cervical cancer cells invasion but also upregulated the level of Zinc finger E‐box binding protein 1 (ZEB1), an EMT-related protein. The induction of ZEB1 could be counteracted by miR-1179 overexpression. It was observed that in cervical cancer patients’ tissues, miR-1179 was downregulated while the pathway of CHAF1A/ZEB1 was upregulated. In summary, our research indicated that the miR-1179 might regulate CHAF1A/ZEB1 axis and inhibit the invasion of cervical cancer cells.

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Section: Introductionmentioning

confidence: 99%

MiR-1179 is downregulated in cervical cancer and its overexpression suppresses cancer cells invasion by targeting CHAF1A/ZEB1

Zhong

Sang

et al. 2021

Acta Biochim Pol

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“…[32][33][34] CHAF1A was found overexpressed in gastric cancer cell lines and tissue samples and its high expression was predictive of poor outcome. 35 Functional in vitro studies demonstrated that CHAF1A expression promoted gastric cancer cell proliferation by enhancing transcriptional activation of c-MYC and CCND1 genes, through direct binding to their promoter regions. This activation was achieved in concert with TCF4, a mediator of Wnt signalling pathway, suggesting that CHAF1A may act as a co-activator of this important pathway.…”

Section: Discussionmentioning

confidence: 99%

Cell-based siRNA screens highlight triple-negative breast cancer cell epigenetic vulnerability

Gaudeau

Provost

Walsh³

et al. 2021

Int J Sci Rep

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Background: Triple-negative breast cancer (TNBC) is a heterogeneous disease defined by ER-, PR- and HER2-negative phenotype and in most cases, a relatively aggressive clinical behaviour. The lack of specific targeted therapies and low efficiency of currently available chemotherapies spurred several clinical trials in the last few years. Despite encouraging results, TNBC still remains a major unmet medical need that prompted us to explore the role of 863 epigenetic modulators in TNBC cell survival.Methods: A comprehensive siRNA library was screened to explore the role of known epigenetic modulators in TNBC cell viability and growth. The knock-down effect was evaluated for 863 epigenetic genes using 4 siRNAs/gene in two TNBC and a non-TNBC cell lines using ATP-based luminescence and nuclei count image-based assays. Considering siRNA off-target effects, four analysis methods including a classical threshold-based analysis and three ranking methods were applied to determine on-target hits for each screen readout. Hit genes common to both phenotypic readouts highlighted strong epigenetic players involved in TNBC cell survival.Results: Overall, knock-down of many epigenetic modulator genes mitigates cell survival in TNBC and a non-TNBC cell lines depicted from both phenotypic readouts. Interestingly, ranking-based analysis confirmed hit genes identified in threshold-based analysis and also revealed additional hits enabling us to confirm CDK1 and KMT5A as important regulators in TNBC cell viability and growth. Surprisingly, CHAF1A appeared as a new candidate gene involved in TNBC cell survival.Conclusions: Taken together, siRNA epigenetic screening results identified CHAF1A as a novel regulator of TNBC cell survival.

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“…CCND1 overexpression has typically been observed to occur in MM precursors with chromosomal 11 and 14 translocations (Miura et al, 2003; Zhan et al, 2006). In gastric cancer, CCND1 has been shown to directly interact with TCF4 through the Wnt signaling pathway (Zheng et al, 2018), suggesting that other mechanisms of CCND1 overexpression may also occur in MM.…”

Section: Discussionmentioning

confidence: 99%

Gene Co-expression Network and Copy Number Variation Analyses Identify Transcription Factors Associated With Multiple Myeloma Progression

Xiang

Huang

et al. 2019

Front. Genet.

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Multiple myeloma (MM) has two clinical precursor stages of disease: monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM). However, the mechanism of progression is not well understood. Because gene co-expression network analysis is a well-known method for discovering new gene functions and regulatory relationships, we utilized this framework to conduct differential co-expression analysis to identify interesting transcription factors (TFs) in two publicly available datasets. We then used copy number variation (CNV) data from a third public dataset to validate these TFs. First, we identified co-expressed gene modules in two publicly available datasets each containing three conditions: normal, MGUS, and SMM. These modules were assessed for condition-specific gene expression, and then enrichment analysis was conducted on condition-specific modules to identify their biological function and upstream TFs. TFs were assessed for differential gene expression between normal and MM precursors, then validated with CNV analysis to identify candidate genes. Functional enrichment analysis reaffirmed known functional categories in MM pathology, the main one relating to immune function. Enrichment analysis revealed a handful of differentially expressed TFs between normal and either MGUS or SMM in gene expression and/or CNV. Overall, we identified four genes of interest ( MAX , TCF4 , ZNF148 , and ZNF281 ) that aid in our understanding of MM initiation and progression.

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CHAF1A interacts with TCF4 to promote gastric carcinogenesis via upregulation of c-MYC and CCND1 expression

Cited by 32 publications

References 46 publications

MiR-1179 is downregulated in cervical cancer and its overexpression suppresses cancer cells invasion by targeting CHAF1A/ZEB1

MiR-1179 is downregulated in cervical cancer and its overexpression suppresses cancer cells invasion by targeting CHAF1A/ZEB1

Cell-based siRNA screens highlight triple-negative breast cancer cell epigenetic vulnerability

Gene Co-expression Network and Copy Number Variation Analyses Identify Transcription Factors Associated With Multiple Myeloma Progression

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