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UHRF1 regulates global DNA hypomethylation and is associated with poor prognosis in esophageal squamous cell carcinoma

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. Howe...

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Detalles Bibliográficos
Autores principales: Nakamura, Kenichi, Baba, Yoshifumi, Kosumi, Keisuke, Harada, Kazuto, Shigaki, Hironobu, Miyake, Keisuke, Kiyozumi, Yuki, Ohuchi, Mayuko, Kurashige, Junji, Ishimoto, Takatsugu, Iwatsuki, Masaaki, Sakamoto, Yasuo, Yoshida, Naoya, Watanabe, Masayuki, Nakao, Mitsuyoshi, Baba, Hideo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5295392/
https://www.ncbi.nlm.nih.gov/pubmed/27507047
http://dx.doi.org/10.18632/oncotarget.11067
Descripción
Sumario: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.