The comparison of nuclear ubiquitous casein and cyclin-dependent kinases substrate (NUCKS) with Ki67 proliferation marker expression in common skin tumors

Zduniak, Krzysztof; Agrawal, Siddarth; Symonowicz, Krzysztof; Jurczyszyn, Kamil; Ziółkowski, Piotr

doi:10.5114/pjp.2014.42669

Cited by 11 publications

(9 citation statements)

References 31 publications

(38 reference statements)

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“…Our findings are the first to demonstrate the biological function in DSBR for NUCKS1. Our results are of particular interest in the context of several expression-array studies that report on the altered expression of NUCKS1 mRNA and protein levels in various types of cancer ( 20 – 27 ). We suggest that elevated levels of NUCKS1 may provide a selective advantage in precancerous cells and during cancer development by overcoming the consequences of replication stress, which leads to DSBs and genomic instability ( 32 , 33 ).…”

Section: Introductionmentioning

confidence: 76%

NUCKS1 is a novel RAD51AP1 paralog important for homologous recombination and genome stability

et al. 2015

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NUCKS1 (nuclear casein kinase and cyclin-dependent kinase substrate 1) is a 27 kD chromosomal, vertebrate-specific protein, for which limited functional data exist. Here, we demonstrate that NUCKS1 shares extensive sequence homology with RAD51AP1 (RAD51 associated protein 1), suggesting that these two proteins are paralogs. Similar to the phenotypic effects of RAD51AP1 knockdown, we find that depletion of NUCKS1 in human cells impairs DNA repair by homologous recombination (HR) and chromosome stability. Depletion of NUCKS1 also results in greatly increased cellular sensitivity to mitomycin C (MMC), and in increased levels of spontaneous and MMC-induced chromatid breaks. NUCKS1 is critical to maintaining wild type HR capacity, and, as observed for a number of proteins involved in the HR pathway, functional loss of NUCKS1 leads to a slow down in DNA replication fork progression with a concomitant increase in the utilization of new replication origins. Interestingly, recombinant NUCKS1 shares the same DNA binding preference as RAD51AP1, but binds to DNA with reduced affinity when compared to RAD51AP1. Our results show that NUCKS1 is a chromatin-associated protein with a role in the DNA damage response and in HR, a DNA repair pathway critical for tumor suppression.

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Section: Introductionmentioning

confidence: 76%

NUCKS1 is a novel RAD51AP1 paralog important for homologous recombination and genome stability

et al. 2015

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“…Besides, NUCKS1 had been shown to be a key transcriptional regulator and chromatin modi er and it could be a potential bio-marker for human diseases, including cancers and metabolic diseases [18]. Similar to the high-mobility group (HMG) proteins, NUCKS1 belonged to the most modi ed proteins in the proteome of mammals and was associated with the progression and diagnosis of human cancer [19]. A study carried out by Kikuchi et al demonstrated that the mRNA and protein expression levels of NUCKS1 were signi cantly up-regulated in colorectal cancer (CRC) tissues compared to that in normal tissues [20].…”

Section: Discussionmentioning

confidence: 99%

NUCKS1 Acts As A Promising Novel Bio-Marker in The Prognosis of Patients with Hepatocellular Carcinoma

Zhang

et al. 2020

Preprint

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Background: Nuclear casein kinase and cyclin-dependent kinase substrate 1 (NUCKS1) was over-expressed in some tumors, including hepatocellular carcinoma (HCC). However, the clinical significance of NUCKS1 in HCC was still unclear. The aim of this study was to explore the expression and prognostic value of NUCKS1 in HCC. Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the relative mRNA expression of NUCKS1 in HCC tissues and corresponding adjacent normal tissues. The relationship between NUCKS1 expression and clinical characteristics of patients was analyzed by c2 test. Kaplan-Meier method and cox regression analysis were applied to estimate the prognostic value of NUCKS1 in HCC. Results: Compared with normal tissues, the relative mRNA expression level of NUCKS1 was significantly up-regulated in HCC tissues (P < 0.001). And high NUCKS1 expression was closely associated with tumor differentiation, TNM stage, vascular invasion and metastasis (P < 0.05). Kaplan-Meier analysis revealed that the overall survival of HCC patients with low expression of NUCKS1 was obviously longer than those with high NUCKS1 expression (log rank test, P = 0.001). NUCKS1 was an independent prognostic factor of HCC patients via univariate and multivariate cox regression analyses.Conclusions: NUCKS1 may be correlated with the progression of HCC and may serve as a potential factor for the prognosis of this disease.

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“…Increased NUCKS expression has been reported in several cancers, [11][12][13][14][15][16][17][18]21 including OC. 9 However, the dynamic and complex phosphorylation of NUCKS implies that NUCKS has the possibility to interact with several binding partners and hence being involved in multiple biological functions.…”

Section: Discussionmentioning

confidence: 99%

“…8 Furthermore, NUCKS is implicated in tumorigenesis, proliferation, invasion, and prognosis of many human malignancies. 9–17 Our previous study had reported that NUCKS overexpressed in endometrial cancer and played a role in predicting prognosis and recurrence. 18 However, up to date, there have been no published reports evaluating its expression in OC tissues and the clinical significance in OC patients.…”

Section: Introductionmentioning

confidence: 99%

NUCKS nuclear elevated expression indicates progression and prognosis of ovarian cancer

et al. 2017

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NUCKS (nuclear, casein kinase, and cyclin-dependent kinase substrate) is implicated in the tumorigenesis of several human malignancies, but its role in ovarian cancer remains unknown. We aim to investigate NUCKS expression and its clinical significance in ovarian cancer. The messenger RNA expression of NUCKS was determined in normal and malignant ovarian tissues using quantitative polymerase chain reaction assay. Immunohistochemistry was applied to detect the status of NUCKS protein expression in 121 ovarian cancer tissues. NUCKS protein high expression was detected in 52 (43.0%) of 121 patients. NUCKS messenger RNA expression was gradually upregulated in non-metastatic ovarian cancers ( n = 20), metastatic ovarian cancers ( n = 20), and its matched metastatic lesions ( n = 20) in comparison with that in normal ovarian tissues ( n = 10; p < 0.05). Elevated expression of NUCKS in ovarian cancer was associated significantly with the Federation of Gynecology and Obstetrics stage ( p = 0.037), histological grade ( p = 0.003), residual disease ( p = 0.013), lymph node metastasis ( p = 0.002), response to chemotherapy ( p < 0.001), and recurrence ( p = 0.013). In the multivariate Cox analysis, NUCKS expression was an independent prognostic marker for overall survival and disease-free survival in ovarian cancer with p values of <0.001 for both. Especially, NUCKS overexpression had prognostic potential for overall survival and disease-free survival ( p < 0.001 for both) in advanced ovarian cancers and only for disease-free survival in early ovarian cancers ( p = 0.017). Our data suggest that NUCKS overexpression may contribute to progression and poor prognosis in ovarian cancer especially in advanced ovarian cancer.

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The comparison of nuclear ubiquitous casein and cyclin-dependent kinases substrate (NUCKS) with Ki67 proliferation marker expression in common skin tumors

Cited by 11 publications

References 31 publications

NUCKS1 is a novel RAD51AP1 paralog important for homologous recombination and genome stability

NUCKS1 is a novel RAD51AP1 paralog important for homologous recombination and genome stability

NUCKS1 Acts As A Promising Novel Bio-Marker in The Prognosis of Patients with Hepatocellular Carcinoma

NUCKS nuclear elevated expression indicates progression and prognosis of ovarian cancer

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