Interplay of Genetic and Epigenetic Alterations in Hepatocellular Carcinoma

Lee, Sun Min; Kim-Ha, Jeongsil; Choi, Won Young; Lee, Jungwoo; Kim, Dawon; Lee, JinYoung; Choi, Eunji; Kim, Young-Joon

doi:10.2217/epi-2016-0027

Cited by 41 publications

(34 citation statements)

References 78 publications

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“…Asian and African countries, especially China, generally show a predominance of HBV . For HBV‐related HCC, it is believed that both genetic and epigenetic alterations play vital roles in hepatocarcinogenesis through direct and indirect mechanisms initiated by HBV …”

mentioning

confidence: 99%

Global DNA 5‐Hydroxymethylcytosine and 5‐Formylcytosine Contents Are Decreased in the Early Stage of Hepatocellular Carcinoma

Liu

Jiang

et al. 2019

Hepatology

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confidence: 99%

Global DNA 5‐Hydroxymethylcytosine and 5‐Formylcytosine Contents Are Decreased in the Early Stage of Hepatocellular Carcinoma

Liu

Jiang

et al. 2019

Hepatology

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“…1,2 The most common epigenetic change associated with human cancers is in DNA methylation, which includes site-specific CpG island promoter hypermethylation and global DNA hypomethylation. 3 Interestingly, global hypomethylation has recently been postulated to be an important contributor to hepatocarcinogenesis.…”

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confidence: 99%

Global Level of Plasma DNA Methylation is Associated with Overall Survival in Patients with Hepatocellular Carcinoma

et al. 2017

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Background The impact of folate deficiency on global DNA methylation is uncertain. It also is unclear whether global DNA methylation is associated with outcome in HCC. LINE-1 methylation levels, as a surrogate marker of global methylation, may be influenced by folate deficiency. However, the interaction between LINE-1 methylation and folate level on overall survival (OS) in hepatocellular carcinoma (HCC) patients is unknown. We evaluated whether LINE-1 hypomethylation and folate deficiency are associated with HCC prognosis. Methods We prospectively recruited 172 HCC patients between 2008 and 2012. LINE-1 methylation levels in plasma and white blood cells (WBC) were measured by pyrosequencing, and plasma folate levels by a radioprotein-binding assay. Results Patients with plasma LINE-1 methylation <70.0% (hypomethylation) had significantly worse OS compared with those with ≥70.0% methylation (hypermethylation) [hazard ratio (HR) = 1.77; 95% confidence interval (CI) 1.12–2.79; P = 0.015]. HCC patients with lower plasma folate levels also had worse survival (<27.7 vs. ≥27.7 nmol/L; HR = 1.96; 95% CI, 1.24–3.09; P = 0.004). Furthermore, survival was poor in patients in whom both plasma LINE-1 methylation and folate levels were low compared with those patients in whom both levels were high (HR = 3.36; 95%CI, 1.77–6.40; P <0.001). This interaction neared statistical significance (P = 0.057). No significant association was found between WBC LINE-1 methylation levels and survival. Conclusions These findings suggest that both lower plasma levels of LINE-1 methylation and folate are associated with worse survival in HCC patients.

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“…The tumorigenesis of HCC is regulated by the interactions between genetic and epigenetic mutations . Gene silencing mediated by lncRNAs is a prevalent epigenetic change in tumorigenesis .…”

Section: Discussionmentioning

confidence: 99%

Long non‐coding RNA SUMO1P3 promotes hepatocellular carcinoma progression through activating Wnt/β‐catenin signalling pathway by targeting miR‐320a

Chen

Lin

et al. 2020

J Cellular Molecular Medi

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In this study, we aimed to investigate expression profile of long non‐coding RNA (lncRNA) SUMO1P3, and its role and molecular mechanisms in the progression of hepatocellular carcinoma (HCC). The expression of SUMO1P3 in HCC tissues and cells was detected using quantitative real‐time polymerase chain reaction (qRT‐PCR). The chi‐squared test was used to estimate the relationship between SUMO1P3 levels and clinical characteristics of HCC cases. Cellular biological behaviours were investigated using MTT, transwell assays and wound healing assay. Bioinformatics and dual‐luciferase reporter assays were performed to identify potential target of SUMO1P3 in HCC. Additionally, protein analysis was carried out using Western blot. The expression of SUMO1P3 was significantly higher in HCC tissues and cells than in non‐cancerous specimens and normal cells (P < .01). Moreover, its up‐regulation was closely correlated with lymph node metastasis (P = .027) and TNM stage (P = .019). SUMO1P3 knockdown inhibited the proliferation, migration and invasion of HCC cells. MiR‐320a was a potential target of SUMO1P3, and its expression was negatively regulated by SUMO1P3 in HCC SUMO1P3 could activate Wnt/β‐catenin pathway, which was mediated by miR‐320a. Elevated expression of SUMO1P3 predicts malignant progression among HCC patients. SUMO1P3 enhances Wnt/β‐catenin pathway through sponging miR‐320a, thus contributing to aggressive progression of HCC.

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Interplay of Genetic and Epigenetic Alterations in Hepatocellular Carcinoma

Cited by 41 publications

References 78 publications

Global DNA 5‐Hydroxymethylcytosine and 5‐Formylcytosine Contents Are Decreased in the Early Stage of Hepatocellular Carcinoma

Global DNA 5‐Hydroxymethylcytosine and 5‐Formylcytosine Contents Are Decreased in the Early Stage of Hepatocellular Carcinoma

Global Level of Plasma DNA Methylation is Associated with Overall Survival in Patients with Hepatocellular Carcinoma

Long non‐coding RNA SUMO1P3 promotes hepatocellular carcinoma progression through activating Wnt/β‐catenin signalling pathway by targeting miR‐320a

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