Abstract:
:Holliday junction recognition protein (HJURP) refers to a histone H3 chaperone that has been implicated in different kinds of malignancies. Yet, its character in pancreatic cancer remains unclear. The expression of HJURP was assessed in PDAC tissues by RT-qPCR, immunoblotting, and immunohistochemistry. HJURP-deficient or overexpressed PDAC cell lines were constructed, using shRNA or plasmids with HJURP insert. MTT, sphere formation assay, migration, and invasion assays were performed to evaluate the viability, proliferation, migration, and invasion of PDAC cells. We used xenograft mice models to assess the tumor growth and metastasis in vivo. RNA-seq was applicated in search of the potential downstream target of HJURP in PDAC and subsequent verification were fulfilled via multiple assays, including immunofluorescence. Additionally, chromatin immunoprecipitation and luciferase reporter assay were conducted to explore the potential regulation of MDM2 expression by HJURP through H3K4me2. In this current research, we found that the expression of HJURP in PDAC cells and tissue was significantly higher than those of adjacent normal tissue, and high HJURP expression predicted poor survival. HJURP significantly promoted the viability, sphere formation, migration, and invasion of PDAC cells in vitro, HJURP also facilitated tumor growth and metastasis in vivo. Mechanically, MDM2/p53 axis is critical for HJURP-mediated malignant behaviors in PDAC, and HJURP regulates MDM2 expression through H3K4me2. HJURP could serve as a promising biomarker, and target for PDAC prognosis and treatment.
journal_name
Cell Death Disjournal_title
Cell death & diseaseauthors
Wang CJ,Li X,Shi P,Ding HY,Liu YP,Li T,Lin PP,Wang YS,Zhang GQ,Cao Ydoi
10.1038/s41419-020-2595-9subject
Has Abstractpub_date
2020-05-21 00:00:00pages
386issue
5issn
2041-4889pii
10.1038/s41419-020-2595-9journal_volume
11pub_type
杂志文章abstract::We previously showed that injury by partial duct ligation (PDL) in adult mouse pancreas activates Neurogenin 3 (Ngn3)(+) progenitor cells that can differentiate to β cells ex vivo. Here we evaluate the role of Ngn3(+) cells in β cell expansion in situ. PDL not only induced doubling of the β cell volume but also increa...
journal_title:Cell death & disease
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journal_title:Cell death & disease
pub_type: 杂志文章,评审
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journal_title:Cell death & disease
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journal_title:Cell death & disease
pub_type: 杂志文章
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journal_title:Cell death & disease
pub_type: 杂志文章
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journal_title:Cell death & disease
pub_type: 杂志文章,评审
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journal_title:Cell death & disease
pub_type: 已发布勘误
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更新日期:2019-10-22 00:00:00
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journal_title:Cell death & disease
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pub_type: 杂志文章
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journal_title:Cell death & disease
pub_type: 杂志文章
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journal_title:Cell death & disease
pub_type: 杂志文章,收录出版
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journal_title:Cell death & disease
pub_type: 杂志文章
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journal_title:Cell death & disease
pub_type: 杂志文章
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journal_title:Cell death & disease
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journal_title:Cell death & disease
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journal_title:Cell death & disease
pub_type: 杂志文章
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pub_type: 已发布勘误
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journal_title:Cell death & disease
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journal_title:Cell death & disease
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