Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.30.2 (endonuclease)
 18,621 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Mus81 gene encodes a critical endonuclease involved in DNA repair and tumor suppression. Our previous study has shown reduced expression of Mus81 in hepatocellular carcinoma and its association with the metastatic potential and prognosis of hepatocellular carcinoma. However, the role of Mus81 in colorectal carcinoma is currently unknown. We therefore carried out the present study to explore the correlation between Mus81 expression and the progression of colorectal carcinoma. Mus81 expression in 92 cases of colorectal carcinoma and matched normal tissues was determined by quantitative real-time polymerase chain reaction. Our results showed that Mus81 expression in colorectal carcinoma tissues was significantly reduced compared with the corresponding normal tissues (P < 0.001) and the downregulation of Mus81 (decreased by more than 50%) was found in 60.9% (56/92) of colorectal carcinoma. Moreover, Mus81 downregulation correlated significantly to hepatic metastasis (P = 0.019) and a high TNM stage (P = 0.025) of colorectal carcinoma. In addition, the decrease of Mus81 was also detected in 10 cases of hepatic metastasis tissues compared with the corresponding primary colorectal carcinoma tissues (P = 0.016). More importantly, colorectal carcinoma patients with apparent Mus81 downregulation have shown significantly poorer overall survival than those with little Mus81 downregulation (P = 0.0374). Also, multivariable Cox regression analysis identified Mus81 downregulation as an independent prognostic factor for colorectal carcinoma (hazard ratio, 1.678; P = 0.040). In conclusion, the reduced expression of Mus81 is closely related to hepatic metastasis and poor prognosis of colorectal carcinoma, indicating Mus81 as a novel prognostic marker for colorectal carcinoma.
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PMID:Downregulation of Mus81 as a novel prognostic biomarker for patients with colorectal carcinoma. 2117 91

Altered DNA repair can be associated with aggressive tumor biology and impact on survival of cancer patients. We investigated whether genetic variation of human apurinic/apyrimidinic (AP) endonuclease, a key multifunctional gene involved in the base excision repair pathway, would play a role in gastric cancer survival outcomes. We genotyped APE1 rs1760944 by the TaqMan method in 925 gastric cancer patients. Analyses of association between the polymorphism and survival outcomes were carried out using the Kaplan-Meier method, Cox proportional hazards models, and the log-rank test. Survival analyses for all patients showed that the differences in median survival time between gastric cancer carriers with APE1 rs1760944 TT (55 months) and those with GT/GG (78 months), were statistically significant (P = 0.025, log-rank test). Kaplan-Meier survival estimates revealed that gastric cancer patients carrying the GT/GG genotypes had a higher survival than TT, and this protective effect was also more pronounced among subgroups with tumor size >5 cm (hazard ratio = 0.66, 95% confidence interval = 0.49-0.88), diffuse-type gastric cancer (0.76, 0.60-0.97), T3 depth of invasion (0.73, 0.57-0.93), lymph node metastasis (0.73, 0.58-0.92), no distant metastasis (0.81, 0.66-0.99), and TNM stage III and IV (0.75, 0.58-0.99 for stage III; 0.50, 0.29-0.88 for stage IV). Our results showed that the genetic variant rs1760944 in APE1 was associated with gastric cancer survival in a Chinese population. Larger studies are needed to verify our findings in different populations.
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PMID:A genetic variation in APE1 is associated with gastric cancer survival in a Chinese population. 2161 20

As a DNA repair protein, flap endonuclease 1 (FEN1), a structure-specific 5' nuclease, plays pivotal roles in the maturation of Okazaki fragments, long-patch base excision repair, restarting of stalled replication forks and telomere maintenance. FEN1 possesses 5' endonuclease, 5' exonuclease and gap-endonuclease activities, which render it an essential node in maintaining genome fidelity. The aim of this study was to investigate the association between the expression level of FEN1 and gastric cancer and to explore the role of FEN1 in carcinogenesis and the progression of gastric cancer. The mRNA and protein expression of FEN1 in 42 matched pairs of human gastric tumor tissues and corresponding normal tissues were measured by semiquantitative reverse transcription-PCR and immunohistochemical staining. FEN1 expression was downregulated in the SGC-7901 gastric cancer cells following transfection with siRNA targeting the FEN1 gene. Western blot analysis was used to evaluate the protein expression of FEN1 in SGC-7901 human gastric cancer cells in order to verify the transfection efficiency of FEN1 siRNA. Moreover, cell proliferation was analyzed by MTS assay. The apoptosis of the cells was determined by flow cytometry. Our results revealed that FEN1 was overexpressed in gastric cancer in comparison to the corresponding normal gastric tissues (P<0.01). We further confirmed that FEN1 expression has a positive correlation with the degree of differentiation (P=0.027), lymphatic metastasis (P=0.001), tumor size (P=0.026) and TNM stage (P=0.020) of gastric cancer. A high FEN1 expression in SGC-7901 cells can be effectively downregulated by siRNA constructed to target the FEN1 gene. Moreover, the inhibition of FEN1 expression suppressed the proliferation and induced the apoptosis of SGC-7901 cells. Taken together, our results indicate that FEN1 may be a promising biomarker for the diagnosis of gastric cancer and individual therapy.
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PMID:Flap endonuclease 1 is a promising candidate biomarker in gastric cancer and is involved in cell proliferation and apoptosis. 2459 Apr

This research aimed to investigate the differential expression of apurinic-apyrimidinic endonuclease 1 (APE1) in hepatocellular carcinoma (HCC) tissues and cells and the effects on proliferation and apoptosis of cancer cells. Immunohistochemical techniques were used to detect the expression of APE1 in 80 cases of HCC and the corresponding paracancerous tissue microarrays; meanwhile, Western blots were used to detect the expression of APE1 in both human HCC BEL-7402, BEL-7405, HCC-9204, Hep3B, HepG2, SMMC-7721 and Huh-7 cells, and normal hepatocyte L-02 cells. The relationship between APE1 expression and clinical pathological characteristics of HCC was statistically analyzed. APE1 shRNA vector was constructed in Hep 3B cells to establish a stably transfected cell line, using Western blots to determine the interference efficiency. Cell proliferation activity was detected with MTT assays, while apoptosis was detected with the Annexin V-FITC/PI double-labeling technique. The expression of APE1 in HCC tissues and cells was significantly up-regulated, and its expression was significantly different from TNM staging and histopathological grading. Down-regulation of APE1 expression significantly reduced the proliferative activity and increased the apoptosis rate of Hep 3B cells. In conclusion, APE1 demonstrates cancer progression potential at the clinical, tissue and cell level. It provides a new idea and theoretical basis for APE1-based clinical diagnosis, prognosis determination and molecular targeted therapy in treatment of HCC.
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PMID:Differential expression of APE1 in hepatocellular carcinoma and the effects on proliferation and apoptosis of cancer cells. 3047 52