Holliday junction–recognizing protein promotes cell proliferation and correlates with unfavorable clinical outcome of hepatocellular carcinoma

Abstract

AimTo investigate the expression and clinical significance of Holliday junction–recognizing protein (HJURP) in hepatocellular carcinoma (HCC).MethodsIn this study, we detected the expression of HJURP protein in samples of 164 patients with HCC, and based on this, we divided the patients into two cohorts: high expression of HJURP and low expression of HJURP. We analyzed the correlation between HJURP expression and the clinicopathological factors using chi-square test. Survival significance of HJURP was defined by Kaplan–Meier method and log-rank test, and the independent prognostic factors were identified by Cox regression model. Using function assays of HCC cell lines, we investigated the influence of HJURP on the proliferation of HCC cells.ResultsIn our study, the proportion of patients with high HJURP expression was 25.6%, which was significantly associated with the tumor size and Barcelona clinic liver cancer stage. Univariate analysis confirmed that high HJURP expression was remarkably associated with poorer overall survival rates (P=0.003), as well as tumor number (P=0.016), tumor differentiation (P=0.047), TNM stage (P=0.005), and Barcelona clinic liver cancer stage (P=0.004). Multivariate analysis confirmed that high HJURP expression (P<0.001) acted as an independent prognostic risk factor of unfavorable prognosis. Real-time polymerase chain reaction analysis revealed that the expression of HJURP was significantly higher in HCC tissues than that in the corresponding normal liver tissues. Moreover, we demonstrated that HJURP overexpression could accelerate HCC cell line proliferation, whereas HJURP knockdown could attenuate the proliferation.ConclusionHigh HJURP expression was an independent prognostic biomarker of HCC, predicting poorer prognosis. HJURP also played an important role in HCC cell proliferation.

DNA repair genes in astrocytoma tumorigenesis, progression and therapy resistance

“…Other studies have described the association between HJURP overexpression, combined with additional alterations, and a higher risk of death for GBM patients (de Tayrac et al, 2011;Valente et al, 2013). Moreover, it was also reported that HJURP overexpression has an independent prognostic value for breast (Hu et al, 2010), lung (Kato et al, 2007), liver (Hu et al, 2017) and ovarian cancer patients, reinforcing the involvement of this protein with cancer aggressiveness and poor outcome.…”

HJURP promotes hepatocellular carcinoma proliferation by destabilizing p21 via the MAPK/ERK1/2 and AKT/GSK3β signaling pathways

“…HJURP has been demonstrated to play an important role in human neoplasms [ 7 – 9 , 25 ]. HJURP exhibits oncogenic activity in various cancer types including HCC.…”

“…In cancer, HJURP has been reported to be highly expressed in some malignancies, including HCC, breast cancer, lung cancer, bladder cancer and glioma [ 6 – 11 ]. Hu et al found that HJURP promotes cell proliferation in vitro and that its expression is correlated with unfavorable clinical outcomes in HCC [ 9 ]. Moreover, Huang et al demonstrated that a single nucleotide polymorphism (SNP) of HJURP, i.e.,rs3771333, can predict a higher susceptibility to HCC among Chinese people [ 12 ].…”

Increased Expression of Holliday Junction-Recognizing Protein (HJURP) as an Independent Prognostic Biomarker in Advanced-Stage Serous Ovarian Carcinoma

“…However, activation of HJURP is required for chromosomal stability and is also involved in immortalizing cancer cells [ 7 ]. The aberrant upregulation of HJURP has been reported in several human cancers, including breast cancer [ 9 , 10 ]. These findings support the role of HJURP as both a prognostic biomarker and also as a potential novel therapeutic target for the development of anticancer drugs.…”

“…HJURP has dual roles in DNA repair and chromosome segregation during mitosis, and the ectopic activation of HJURP has been shown to be associated with the immortality of cancer cells [ 7 ]. Overexpression of HJURP has now been reported in hepatocellular carcinoma and breast cancer [ 9 , 10 ]. However, there remains limited understanding on whether HJURP expression is a prognostic biomarker in ovarian cancer, despite continuing reports of HJURP in carcinogenesis.…”