EVI1 promotes cell proliferation in HBx-induced hepatocarcinogenesis as a critical transcription factor regulating lncRNAs

Huang, Jinfeng; Wang, Yue; Liu, Feng; Yin, Lei; Zhao, Chenxi; Guo, Yingjun; Sun, Shuhan

doi:10.18632/oncotarget.7993

Cited by 8 publications

(4 citation statements)

References 39 publications

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“…WRN’s functions are related to its DNA helicase and exonuclease activities, and therefore, it interacts with p53 in DNA replication, repair, and recombination pathways to influence genomic instability[ 33 ]. The functions of MECOM in HCC carcinogenesis are linked with hepatitis B X protein carcinogenesis and antagonized growth inhibition induced by transforming growth factor-β (TGF-β) signaling[ 34 ]. Another CNA-linked gene, ELAC2 , encodes a protein that contributes to endoribonuclease activity for tRNA 3′ processing[ 35 ].…”

Section: Discussionmentioning

confidence: 99%

Prediction of early-stage hepatocellular carcinoma using OncoScan chromosomal copy number aberration data

Lee

et al. 2017

WJG

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AIMTo identify chromosomal copy number aberrations (CNAs) in early-stage hepatocellular carcinoma (HCC) and analyze whether they are correlated with patient prognosis.METHODSOne hundred and twenty patients with early-stage HCC were enrolled in our study, with the collection of formalin fixed, paraffin-embedded (FFPE) specimens and clinicopathological data. Tumor areas were marked by certified pathologists on a hematoxylin and eosin-stained slide, and cancer and adjacent non-cancerous tissues underwent extraction of DNA, which was analyzed with the Affymetrix OncoScan platform to assess CNAs and loss of heterozygosity (LOH). Ten individuals with nonmalignant disease were used as the control group. Another cohort consisting of 40 patients with stage I/II HCC were enrolled to analyze gene expression and to correlate findings with the OncoScan data.RESULTSCopy number amplifications occurred at chromosomes 1q21.1-q44 and 8q12.3-24.3 and deletions were found at 4q13.1-q35.2, 8p 23.2-21.1, 16q23.3-24.3, and 17p13.3-12, while LOH commonly occurred at 1p32.3, 3p21.31, 8p23.2-21.1, 16q22.1-24.3, and 17p 13.3-11 in early-stage HCC. Using Cox regression analysis, we also found that a higher percentage of genome change (≥ 60%) was an independent factor for worse prognosis in early-stage HCC (P = 0.031). Among the 875 genes in the OncoScan GeneChip, six were independent predictors of worse disease-free survival, of which three were amplified (MYC, ELAC2, and SYK) and three were deleted (GAK, MECOM, and WRN). Further, patients with HCC who exhibited ≥ 3 CNAs involving these six genes have worse outcomes compared to those who had < 3 CNAs (P < 0.001). Similarly, Asian patients with stage I HCC from The Cancer Genome Atlas harboring CNAs with these genes were also predicted to have poorer outcomes.CONCLUSIONPatients with early-stage HCC and increased genome change or CNAs involving MYC, ELAC2, SYK, GAK, MECOM, or WRN are at risk for poorer outcome after resection.

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Section: Discussionmentioning

confidence: 99%

Prediction of early-stage hepatocellular carcinoma using OncoScan chromosomal copy number aberration data

Lee

et al. 2017

WJG

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“…Therefore, we focused on proteins that usually function as epigenetic regulators ( Table S7 ). MECOM, a member of the transcriptional regulator family, is of particular interest as it can contribute to the tumorigenesis of HCC 26 , 27 , and displays histone methyltransferase activity in the monomethylation of Lys9 of histone H3 (H3K9me1) in vitro 28 , 29 . Reciprocal co-immunoprecipitation experiments showed that MECOM specifically binds to DDX56 (Figure 7 A), while immunofluorescence experiments demonstrated that DDX56 and MECOM were colocalized in HCC cells (Figure 7 B).…”

Section: Resultsmentioning

confidence: 99%

DDX56 transcriptionally activates MIST1 to facilitate tumorigenesis of HCC through PTEN-AKT signaling

Zhou¹,

Du²,

Wei³

et al. 2022

Theranostics

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Rationale : Hepatocellular carcinoma (HCC) is a primary malignancy of the liver that is the leading cause of cancer-related mortality worldwide. However, genetic alterations and mechanisms underlying HCC development remain unclear. Methods: Tissue specimens were used to evaluate the expression of DEAD-Box 56 (DDX56) to determine its prognostic value. Colony formation, CCK8, and EdU-labelling assays were performed to assess the effects of DDX56 on HCC proliferation. The in vivo role of DDX56 was evaluated using mouse orthotopic liver xenograft and subcutaneous xenograft tumor models. Dual-luciferase reporter, chromatin immunoprecipitation, and electrophoretic mobility shift assays were performed to examine the effect of DDX56 on the MIST1 promoter. Results: DDX56 expression in HCC tissues was elevated and this increase was strongly correlated with poor prognoses for HCC patients. Functionally, DDX56 promoted HCC cell proliferation both in vitro and in vivo , while mechanistically interacting with MECOM to promote HCC proliferation by mono-methylating H3K9 (H3K9me1) on the MIST1 promoter, leading to enhanced MIST1 transcription and subsequent regulation of the PTEN/AKT signaling pathway, which promotes HCC proliferation. More importantly, the PTEN agonist, Oroxin B (OB), blocked the DDX56-mediated PTEN-AKT signaling pathway, suggesting that treating HCC patients with OB may be beneficial as a therapeutic intervention. Furthermore, we observed that ZEB1 bound to DDX56 and transcriptionally activated DDX56, leading to HCC tumorigenesis. Conclusions: Our results indicated that the ZEB1-DDX56-MIST1 axis played a vital role in sustaining the malignant progression of HCC and identified DDX56 as a potential therapeutic target in HCC tumorigenesis.

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“…Upregulated by HBx, WEE2-AS1 is able to accelerate the proliferation, migration, invasion and cell cycle progression of HCC cells through increasing the expression of Fermitin family member 3 (94). Additionally, recent studies have shown that the expression levels of lncRNAs are regulated by HBx (95)(96)(97)(98)(99).…”

Section: Dbh-as1 Dbh-as1mentioning

confidence: 99%

Long non‑coding RNAs in HBV‑related hepatocellular carcinoma (Review)

et al. 2019

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EVI1 promotes cell proliferation in HBx-induced hepatocarcinogenesis as a critical transcription factor regulating lncRNAs

Cited by 8 publications

References 39 publications

Prediction of early-stage hepatocellular carcinoma using OncoScan chromosomal copy number aberration data

Prediction of early-stage hepatocellular carcinoma using OncoScan chromosomal copy number aberration data

DDX56 transcriptionally activates MIST1 to facilitate tumorigenesis of HCC through PTEN-AKT signaling

Long non‑coding RNAs in HBV‑related hepatocellular carcinoma (Review)

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