Objective:To study the LMP2A, AnnexinA2, Rad52 and Gli1 expression in nasopharyngeal carcinoma and their correlation with tumor malignancy.Methods:Nasopharyngeal cancer tissue confirmed by fibreoptic nasopharyngoscopi...Objective:To study the LMP2A, AnnexinA2, Rad52 and Gli1 expression in nasopharyngeal carcinoma and their correlation with tumor malignancy.Methods:Nasopharyngeal cancer tissue confirmed by fibreoptic nasopharyngoscopic biopsy and mild chronic rhinitis mucosa inflammation tissue in Renmin Hospital of Wuhan University between May 2014 and February 2017 were selected to extract the RNA, and then fluorescence quantitative PCR kits were used to determine the expression of LMP2A, AnnexinA2, Rad52, Gli1, epithelial-mesenchymal transition genes and cell cycle genes.Results: LMP2A, AnnexinA2, Rad52 and Gli1 mRNA expression in nasopharyngeal cancer lesions were significantly higher than those in rhinitis mucosa inflammation lesions, and the higher the clinical stage, the higher the LMP2A, AnnexinA2, Rad52 and Gli1 mRNA expression in nasopharyngeal cancer lesions;E-cadherin mRNA expression in nasopharyngeal cancer lesions was significantly lower than that in rhinitis mucosa inflammation lesions and negatively correlated with LMP2A and Gli1 while N-cadherin, Vimentin and ZEB2 mRNA expression were significantly higher than those in rhinitis mucosa inflammation lesions and positively correlated with LMP2A and Gli1;CyclinD1, CyclinE and PCNA mRNA expression in nasopharyngeal cancer lesions were significantly higher than those in rhinitis mucosa inflammation lesions and positively correlated with with AnnexinA2 and Rad52.Conclusion:The high expression of LMP2A, AnnexinA2, Rad52 and Gli1 in nasopharyngeal carcinoma can promote epithelial-mesenchymal transition and cell cycle process in cancer cells.展开更多
Tumors often have DNA repair defects, suggesting additional inhibition of other DNA repair pathways in tumors may lead to synthetic lethality. Accumulating data demonstrate that DNA repair-defective tumors, in particu...Tumors often have DNA repair defects, suggesting additional inhibition of other DNA repair pathways in tumors may lead to synthetic lethality. Accumulating data demonstrate that DNA repair-defective tumors, in particular homologous recombination (HR), are highly sensitive to DNA-damaging agents. Thus, HR-defective tumors exhibit potential vulnerability to the synthetic lethality approach, which may lead to new therapeutic strategies. It is well known that poly (adenosine diphosphate (ADP)-ribose) polymerase (PARP) inhibitors show the synthetically lethal effect in tumors defective in BRCA1 or BRCA2 genes encoded proteins that are required for efficient HR. In this review, we summarize the strategies of targeting DNA repair pathways and other DNA metabolic functions to cause synthetic lethality in HR-defective tumor cells.展开更多
基金Surface Project of Natural Science Foundation of China No:81372407.
文摘Objective:To study the LMP2A, AnnexinA2, Rad52 and Gli1 expression in nasopharyngeal carcinoma and their correlation with tumor malignancy.Methods:Nasopharyngeal cancer tissue confirmed by fibreoptic nasopharyngoscopic biopsy and mild chronic rhinitis mucosa inflammation tissue in Renmin Hospital of Wuhan University between May 2014 and February 2017 were selected to extract the RNA, and then fluorescence quantitative PCR kits were used to determine the expression of LMP2A, AnnexinA2, Rad52, Gli1, epithelial-mesenchymal transition genes and cell cycle genes.Results: LMP2A, AnnexinA2, Rad52 and Gli1 mRNA expression in nasopharyngeal cancer lesions were significantly higher than those in rhinitis mucosa inflammation lesions, and the higher the clinical stage, the higher the LMP2A, AnnexinA2, Rad52 and Gli1 mRNA expression in nasopharyngeal cancer lesions;E-cadherin mRNA expression in nasopharyngeal cancer lesions was significantly lower than that in rhinitis mucosa inflammation lesions and negatively correlated with LMP2A and Gli1 while N-cadherin, Vimentin and ZEB2 mRNA expression were significantly higher than those in rhinitis mucosa inflammation lesions and positively correlated with LMP2A and Gli1;CyclinD1, CyclinE and PCNA mRNA expression in nasopharyngeal cancer lesions were significantly higher than those in rhinitis mucosa inflammation lesions and positively correlated with with AnnexinA2 and Rad52.Conclusion:The high expression of LMP2A, AnnexinA2, Rad52 and Gli1 in nasopharyngeal carcinoma can promote epithelial-mesenchymal transition and cell cycle process in cancer cells.
基金US Public Health Service Grants (Grant No. CA107640, to SNP)"Independent Innovation Foundation of Shandong University IIFSDU" (Grant No. 2010 TB017, to ZF)the National Natural Science Foundation of China (Grant No.81172527, to ZF and SNP) for financial support
文摘Tumors often have DNA repair defects, suggesting additional inhibition of other DNA repair pathways in tumors may lead to synthetic lethality. Accumulating data demonstrate that DNA repair-defective tumors, in particular homologous recombination (HR), are highly sensitive to DNA-damaging agents. Thus, HR-defective tumors exhibit potential vulnerability to the synthetic lethality approach, which may lead to new therapeutic strategies. It is well known that poly (adenosine diphosphate (ADP)-ribose) polymerase (PARP) inhibitors show the synthetically lethal effect in tumors defective in BRCA1 or BRCA2 genes encoded proteins that are required for efficient HR. In this review, we summarize the strategies of targeting DNA repair pathways and other DNA metabolic functions to cause synthetic lethality in HR-defective tumor cells.