The genetic and epigenetic alterations in human hepatocellular carcinoma: a recent update

Liu, Ming; Jiang, Lingxi; Guan, Xin Yuan

doi:10.1007/s13238-014-0065-9

Cited by 145 publications

(125 citation statements)

References 190 publications

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“…The majority of studies regarding HCC have focused on the cellular nucleus, with a number of variations in genes and their expression identified as potential carcinogenesis factors (16,17). However, the true cause of HCC carcinogenesis is yet to be elucidated.…”

Section: Discussionmentioning

confidence: 99%

Associations between sequence variations in the mitochondrial DNA D-loop region and outcome of hepatocellular carcinoma

Wan

Peng

et al. 2016

Oncology Letters

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Abstract. The association between mitochondrial DNA (mtDNA) polymorphisms or mutations and the prognoses of cancer have been investigated previously, but the results have been ambiguous. In the present study, the associations between sequence variations in the mtDNA D-loop region and the outcomes of patients with hepatocellular carcinoma (HCC) were analysed. A total of 140 patients with HCC (123 males and 17 females), who were hospitalised to undergo radical resection, were studied. Polymerase chain reaction and direct sequencing were performed to detect the sequence variations in the mtDNA D-loop region. Multivariate and univariate analyses were conducted to determine important factors in the prognosis of HCC. A total of 150 point sequence variations were observed in the 140 cases (13 point mutations, 8 insertions, 20 deletions and 116 polymorphisms). The variation rate was 13.4% (150/1, 122). mtDNA nucleotide 150 (C/T) was an independent factor in the logistic regression for early/late recurrence of HCC. Patients with 150T appeared to have later recurrences. In a Cox proportional hazards regression model, hepatitis B virus DNA, Child-Pugh class, differentiation degree, tumour-node-metastasis (TNM) stage, nucleotide 16263 (T/C) and nucleotide 315 (N/insertion C) were independent factors for tumour-free survival time. Patients with the 16263T allele had a greater tumour-free survival time than patients with the 16263C allele. Similarly, patients with 315 insertion C had a superior tumour-free survival time when compared with patients with 315 N (normal). In the Cox proportional hazards regression model, recurrence type (early/late), Child-Pugh class, TNM stage and adjuvant treatment after tumour recurrence (none or one/more than one treatment) were independent factors for overall survival. None of the mtDNA variations served as independent factors. Patients with late recurrence, Child-Pugh class A, and low TNM stages and/or those who received more than one adjuvant treatment following tumour recurrence had favourable outcomes. mtDNA D-loop polymorphisms were associated with early recurrence and tumour-free survival time, but not with overall survival. mtDNA D-loop mutations in HCC were infrequent and lacked prognostic utility. The detection of mtDNA D-loop polymorphisms may assist in identifying risk factors for HCC prognosis, particularly for the short-term outcome, thereby aiding the construction of an appropriate therapeutic strategy.

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Section: Discussionmentioning

confidence: 99%

Associations between sequence variations in the mitochondrial DNA D-loop region and outcome of hepatocellular carcinoma

Wan

Peng

et al. 2016

Oncology Letters

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“…Over 100 million people worldwide are exposed to arsenic-contaminated drinking water, making it a global health concern (Polya and Charlet, 2009). Arsenic has been reported to induce epigenetic alterations related to HCC progression (Liu et al, 2014) and to silence hepatic PDK4 expression through activation of histone H3K9 methyltransferase G9a .…”

Section: Introductionmentioning

confidence: 99%

Pyruvate Dehydrogenase Kinase 4 Deficiency Results in Expedited Cellular Proliferation through E2F1-Mediated Increase of Cyclins

Choiniere

Wang

2016

Mol Pharmacol

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Hepatocellular carcinoma (HCC) is a common form of cancer with prevalence worldwide. There are many factors that lead to the development and progression of HCC. This study aimed to identify potential new tumor suppressors, examine their function as cell cycle modulators, and investigate their impact on the cyclin family of proteins and cyclin-dependent kinases (CDKs). In this study, the pyruvate dehydrogenase kinase (PDK)4 gene was shown to have potential tumor suppressor characteristics. PDK4 expression was significantly downregulated in human HCC. Pdk4 2/2 mouse liver exhibited a consistent increase in cell cycle regulator proteins, including cyclin D1, cyclin E1, cyclin A2, some associated CDKs, and transcription factor E2F1.PDK4-knockdown HCC cells also progressed faster through the cell cycle, which concurrently expressed high levels of cyclins and E2F1 as seen in the Pdk4 2/2 mice. Interestingly, the induced cyclin E1 and cyclin A2 caused by Pdk4 deficiency was repressed by arsenic treatment in mouse liver and in HCC cells. E2f1 deficiency in E2f1 2/2 mouse liver or knockdown E2F1 using small hairpin RNAs in HCC cells significantly decreased cyclin E1, cyclin A2, and E2F1 proteins. In contrast, inhibition of PDK4 activity in HCC cells increased cyclin E1, cyclin A2, and E2F1 proteins. These findings demonstrate that PDK4 is a critical regulator of hepatocyte proliferation via E2F1-mediated regulation of cyclins.

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“…Metastatic recurrence is the most important reason for the unsatisfactory prognosis following surgery (4)(5)(6)8,9). Owing to its high incidence, metastasis and mortality rates, HCC has attracted attention for the investigation of the mechanism underlying its occurrence and development.…”

Section: Discussionmentioning

confidence: 99%

“…In total, ~70% of patients experience relapse within five years of undergoing surgery and >80% of recurrences are within the remaining liver tissue (5). Patients with HCC often exhibit various outcomes, even when identical clinicopathological features are observed; this suggests that the development and rapid progression of HCC involves numerous complex molecular and cellular events (6). Therefore, developing effective methods for the prevention and treatment of HCC requires an improved understanding of the biological development of HCC.…”

Section: Introductionmentioning

confidence: 99%

Preliminary investigation of the role of BTB domain-containing 3 gene in the proliferation and metastasis of hepatocellular carcinoma

Xiao

Zhao

et al. 2017

Oncology Letters

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Abstract. Hepatocellular carcinoma (HCC) is one of the leading digestive malignancies, with a high metastasis and recurrence. The development and rapid progression of HCC involves numerous complex molecular and cellular events. Therefore, developing effective methods for the prevention and treatment of HCC requires an improved understanding of the biological development of HCC. In our previous analysis of the tissue microarray data, the BTB domain-containing 3 (BTBD3) gene was upregulated in HCC tissues, indicating that it may be a cancer-associated gene and serve a role in the occurrence and development of HCC. In the present study, reverse transcription-quantitative polymerase chain reaction and western blotting were performed to analyze the expression level of BTBD3 in four HCC cell lines; HepG2, Huh7, Bel7404 and Hep3B. The overexpression of BTBD3 in the four cell lines confirmed that BTBD3 was a cancer-associated gene. Subsequently, a short interfering RNA interference technique was performed to investigate the effect of BTBD3 expression on the proliferation and metastasis of Bel7407 cells. MTS assay and flow cytometry were used to evaluate the effect of BTBD3 on the proliferation and cell cycle, and a scratch test and Transwell assay were performed to determine the alterations to the migration and invasion of cancer cells. The results revealed that there was a minimal impact on cell proliferation following silencing of the BTBD3 gene. However, significant inhibition of cell invasion was demonstrated in the scratch test and the Transwell model. Based on these results, it was suggested that BTBD3 gene may be overexpressed in HCC tissues and cell lines, which promotes the invasion and metastasis of cancer cells without affecting cell proliferation.

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The genetic and epigenetic alterations in human hepatocellular carcinoma: a recent update

Cited by 145 publications

References 190 publications

Associations between sequence variations in the mitochondrial DNA D-loop region and outcome of hepatocellular carcinoma

Associations between sequence variations in the mitochondrial DNA D-loop region and outcome of hepatocellular carcinoma

Pyruvate Dehydrogenase Kinase 4 Deficiency Results in Expedited Cellular Proliferation through E2F1-Mediated Increase of Cyclins

Preliminary investigation of the role of BTB domain-containing 3 gene in the proliferation and metastasis of hepatocellular carcinoma

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