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.
Highlights
Pancreatic cancer is one of the most lethal malignancies, ranking seventh highest cause of cancer death worldwide[1]
Omnibus (GEO) datasets (GSE16515, GSE28735, and GSE15471) showed increased Holliday junction recognition protein (HJURP) expression in pancreatic ductal adenocarcinoma (PDAC) compared to normal tissues samples (Fig. 1a–c)
HJURP has been demonstrated to be correlated with multiple human neoplasms, including bladder, breast, liver, and lung cancer, as well as glioma[9,10,11,12,13]
Summary
Pancreatic cancer is one of the most lethal malignancies, ranking seventh highest cause of cancer death worldwide[1]. Pancreatic ductal adenocarcinoma (PDAC) is the most common malignancy of the pancreas, with an estimated 458,918 new cases diagnosed globally in 2018 and an associated 432,242 deaths in the same year[2]. Official journal of the Cell Death Differentiation Association. Wang et al Cell Death and Disease (2020)11:386 of chromatin structure and function, they are found to be frequently misregulated in cancer, which can have profound consequences on tumor growth and survival[5]. Holliday junction recognition protein (HJURP) is a histone H3 chaperone, responsible for CENP-A deposition at human centromeres during late mitosis/early G1
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