RRC ID 64568
著者 Nakamura K, Baba Y, Kosumi K, Harada K, Shigaki H, Miyake K, Kiyozumi Y, Ohuchi M, Kurashige J, Ishimoto T, Iwatsuki M, Sakamoto Y, Yoshida N, Watanabe M, Nakao M, Baba H.
タイトル UHRF1 regulates global DNA hypomethylation and is associated with poor prognosis in esophageal squamous cell carcinoma.
ジャーナル Oncotarget
Abstract BACKGROUND:Global DNA hypomethylation contributes to oncogenesis through various mechanisms. The level of long interspersed nucleotide element-1 (LINE- 1) methylation is considered a surrogate marker of global DNA methylation, and is attracting interest as a good predictor of cancer prognosis. However, the mechanism how LINE-1 (global DNA) methylation is controlled in cancer cells remains to be fully elucidated. Ubiquitin-like with PHD and RING finger domain 1 (UHRF1) plays a crucial role in DNA methylation. UHRF1 is overexpressed in many cancers, and UHRF1 overexpression may be a mechanism underlying DNA hypomethylation in cancer cells. Nonetheless, the relationship between UHRF1, LINE-1 methylation level, and clinical outcome in esophageal squamous cell carcinoma (ESCC) remains unclear.
RESULTS:In ESCC cell lines, vector-mediated UHRF1 overexpression caused global DNA (LINE-1) hypomethylation and, conversely, UHRF1 knockdown using siRNA increased the global DNA methylation level. In ESCC tissues, UHRF1 expression was significantly associated with LINE-1 methylation levels. Furthermore, UHRF1 overexpression correlated with poor prognosis in our cohort of 160 ESCC patients.
MATERIALS AND METHODS:The relationships between UHRF1 expression and LINE-1 methylation level (i.e., global DNA methylation level) were investigated using ESCC tissues and cell lines. In addition, we examined the correlation between UHRF1 expression, LINE-1 methylation, and clinical outcome in patients with ESCC.
CONCLUSIONS:Our results suggest that UHRF1 is a key epigenetic regulator of DNA methylation and might be a potential target for cancer treatment.
巻・号 7(36)
ページ 57821-57831
公開日 2016-9-6
DOI 10.18632/oncotarget.11067
PII 11067
PMID 27507047
PMC PMC5295392
MeSH Aged Azacitidine / chemistry Biomarkers, Tumor / genetics CCAAT-Enhancer-Binding Proteins / genetics CCAAT-Enhancer-Binding Proteins / metabolism* Carcinoma, Squamous Cell / diagnosis Carcinoma, Squamous Cell / genetics Carcinoma, Squamous Cell / metabolism* Cell Transformation, Neoplastic / genetics DNA Methylation* Disease-Free Survival Epigenesis, Genetic Epigenomics Esophageal Neoplasms / diagnosis Esophageal Neoplasms / genetics Esophageal Neoplasms / metabolism* Esophageal Squamous Cell Carcinoma Esophagus / metabolism Female Humans Long Interspersed Nucleotide Elements Male Middle Aged Prognosis Proportional Hazards Models Sequence Analysis, DNA Treatment Outcome Ubiquitin / chemistry Ubiquitin-Protein Ligases
IF 5.168
リソース情報
ヒト・動物細胞 TE-1(RCB1894) TE-4(RCB2097) TE-6(RCB1950) TE-8(RCB2098) TE-9(RCB1988) TE-10(RCB2099) TE-11(RCB2100) TE-14(RCB2101) TE-15(RCB1951)