Overexpression of KIAA0101 predicts poor prognosis in primary lung cancer patients.
ABSTRACT High expression of KIAA0101 (p15(PAF)/OEATC-1) which contains a proliferating cell nuclear antigen (PCNA)-binding motif, a key factor in DNA repair and/or apoptosis and cell cycle regulation, has been observed in a variety of human malignancies. The aim of this study was to observe the expression of KIAA0101 in human non-small-cell lung cancer (NSCLC), explore its clinicopathological significance and evaluate KIAA0101 expression as a potential prognostic marker. KIAA0101 transcript was found to be overexpressed in the great majority of lung cancers by semi-quantitative RT-PCR. A total of 357 NSCLCs were analyzed immunohistochemically on tissue microarrays. High-level KIAA0101 expression was observed in 33.9% (121 of 357 cases), and correlated with male gender (P<0.0001), tumor progression (pT status) (P=0.0008), lymph node metastasis (pN status) (P=0.0003), non-adenocarcinoma histological classification (P<0.0001), and smoking history (P<0.0001), but not with patient age or pleural invasion. Patients with tumors displaying high-level KIAA0101 expression showed significantly shorter survival (P<0.0001, log-rank test). Similarly, gender, pT status, pN status, pleural invasion, histological classification, and smoking history were significant prognostic markers in univariate Cox survival analysis. Importantly, high-level KIAA0101 expression was also identified as an independent prognostic factor by multivariate analysis (P=0.0320). These results provide additional information for determining postoperative adjuvant treatment of NSCLC.
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ABSTRACT: Proliferating cell nuclear antigen (PCNA)-Associated Factor (PAF15) is a small protein containing a PCNA interacting motif and sequences for association with ubiquitin enzymes. In interaction with PCNA, PAF15 plays a key role in recruiting DNA replicative polymerase by double monoubiquitination at Lys(15) and Lys(24). Under DNA damage conditions, PAF15 regulates the switch from DNA replicative polymerase to translesion synthesis polymerase in order to bypass the replication-blocking lesions. Overexpression of PAF15 promotes the repair of ultraviolet-induced DNA damage and prevents cell death, whereas attenuation of PAF15 decreases DNA replication and cell survival. Ectopic expression of PAF15 in mouse fibroblasts increases colony formation and tumourigenicity. PAF15 is aberrantly increased in various human malignancies with poor prognosis. Collectively, PAF15 may contribute to carcinogenesis and represents one of the potential therapeutic targets in the treatment of cancer.The international journal of biochemistry & cell biology 03/2014; · 4.89 Impact Factor
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ABSTRACT: Autophagy has been shown to facilitate replication of hepatitis C virus (HCV); however, the mechanism by which HCV induces autophagy has not been fully established. NS5A, a nonstructural protein expressed by HCV, regulates numerous cellular pathways, including autophagy, by up-regulating Beclin 1; however, the underlying mechanism remains unclear. To obtain new insights into HCV-regulated autophagy, NS5ATP9 was overexpressed in HepG2 and L02 cells, resulting in up-regulation of endogenous Beclin 1 mRNA and protein levels, respectively. The luciferase-reporter assay results showed that both NS5A and NS5ATP9 could transactivate Beclin 1 promoter activity, but that NS5A could not transactivate the Beclin 1 promoter in NS5ATP9-silenced HepG2 and L02 cells. Up-regulation of Beclin 1 mRNA and protein expression by NS5A could also be attenuated by NS5ATP9 knock-down. Furthermore, the HepG2 and L02 cells that transiently overexpressed NS5ATP9 had enhanced accumulation of vacuoles carrying the autophagy marker LC3, consistent with the conversion of endogenous LC3-I to LC3-II. In contrast, the conversion of endogenous LC3-I to LC3-II could not be enhanced by NS5A in NS5ATP9-silenced HepG2 cells. These results highlight an important potential role for NS5ATP9 in HCV NS5A-induced hepatocyte autophagy.Journal of Viral Hepatitis 08/2013; 21(6). · 3.08 Impact Factor
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ABSTRACT: The prognosis for gastric cancer is poor; therefore, there is urgent need for the development of novel, especially noninvasive surrogate biomarkers. NS5ATP9 is significantly overexpressed in gastric cancer tissues, and altered NS5ATP9 expression in human gastric cancer is associated with tumor recurrence. This study aimed to determine whether a correlation exists between NS5ATP9 mRNA levels in peripheral blood mononuclear cells (PBMCs) and gastric cancer prognosis in patients. NS5ATP9 mRNA levels were assessed by real-time RT-PCR in PBMC samples obtained from 207 gastric cancer patients, 47 patients with benign gastric lesions, and 78 healthy individuals. In addition, NS5ATP9 protein expression was evaluated by Western blot in PBMC samples from 30 gastric cancer patients and 30 healthy individuals, chosen randomly. Finally, clinicopathological data and survival of all gastric cancer patients were collected and analyzed. NS5ATP9 in PBMCs from gastric cancer patients was significantly upregulated both at mRNA and protein levels. Interestingly, NS5ATP9 mRNA overexpression in PBMCs was significantly associated with poor disease-free survival and overall survival of cancer patients, but not with tumor recurrence. Multivariate analysis showed NS5ATP9 mRNA levels and tumor lymph node metastasis were independent correlation with 3-year survival rate. Importantly, the diagnostic sensitivity and specificity (70.6 and 79.5 %, respectively) were higher for NS5ATP9 mRNA in PBMCs compared with the serum tumor markers CEA (45.0 and 84.6 %, respectively) and CA19-9 (61.5 and 69.2 %, respectively). These findings suggested that NS5ATP9 mRNA levels in PBMCs can be used for prognosis in gastric cancer patients.Medical Oncology 08/2014; 31(8):106. · 2.06 Impact Factor