Xeroderma pigmentosum group D (XPD) gene is the second subunit of basic transcript factor TFII H; it plays an important role in transcription and nucleotide excision repair. In this study, using the total RNA extracted from HeLa cells, we cloned the human full length XPD by RT-PCR and inserted it into the pEGFP-N2 plasmid vector which expressed the green fluorescence protein (GFP). Then the recombinant plasmid pEGFP-N2/XPD was transfected into the human hepatoma carcinoma cell Hep3B integrated with HBx protein,and we analysed the expression of HBx and the proliferative ability of recombinant cells. The data collected from this study could serve as a physical basis on which to further investigate the biological activities of XPD.
Cloning, Molecular ; DNA Repair ; Female ; HeLa Cells ; Humans ; Liver Neoplasms ; genetics ; Recombinant Proteins ; genetics ; metabolism ; Trans-Activators ; genetics ; Transcription Factor TFIIH ; genetics ; Transcription, Genetic ; Transfection ; Viral Regulatory and Accessory Proteins ; genetics ; Xeroderma Pigmentosum Group D Protein ; genetics ; metabolism

Ovarian cancer is the leading cause of death in women worldwide. Cisplatin is the core of first-line chemotherapy for patients with advanced ovarian cancer. Many patients eventually become resistant to cisplatin, diminishing its therapeutic effect. MicroRNAs (miRNAs) have critical functions in diverse biological processes. Using miRNA profiling and polymerase chain reaction validation, we identified a panel of differentially expressed miRNAs and their potential targets in cisplatin-resistant SKOV3/DDP ovarian cancer cells relative to cisplatin-sensitive SKOV3 parental cells. More specifically, our results revealed significant changes in the expression of 13 of 663 miRNAs analyzed, including 11 that were up-regulated and 2 that were down-regulated in SKOV3/DDP cells with or without cisplatin treatment compared with SKOV3 cells with or without cisplatin treatment. miRNA array and mRNA array data were further analyzed using Ingenuity Pathway Analysis software. Bioinformatics analysis suggests that the genes ANKRD17, SMC1A, SUMO1, GTF2H1, and TP73, which are involved in DNA damage signaling pathways, are potential targets of miRNAs in promoting cisplatin resistance. This study highlights candidate miRNA-mRNA interactions that may contribute to cisplatin resistance in ovarian cancer.
Cell Cycle Proteins ; Cell Line, Tumor ; Chromosomal Proteins, Non-Histone ; Cisplatin ; Cysteine Endopeptidases ; DNA-Binding Proteins ; Down-Regulation ; Drug Resistance, Neoplasm ; Endopeptidases ; Female ; Humans ; MicroRNAs ; Nuclear Proteins ; Ovarian Neoplasms ; Phosphoproteins ; RNA, Messenger ; Signal Transduction ; Transcription Factors, TFII ; Tumor Protein p73 ; Tumor Suppressor Proteins ; Up-Regulation

BACKGROUND AND OBJECTIVEIt has been proven that close relation was existed between XPD polymorphism G312A and lung cancer risk. However, some of the results are not consistent. The aim of this study is to explore the impact of DNA repair gene XPD polymorphism G312A on lung cancer risk.

METHODSThe literatures eligible from PUBMED, EMBASE, CNKI and WANGFANG database were enrolled in the meta-analysis. Heterogeneity among combined studies was assessed. The pooled OR and 95%CI were calculated. The sensitivity analysis and the publication bias were evaluated by RevMan 5.0 and STATA 11.0.

RESULTSThere were 6554 cases and 8322 controls from 18 studies included in the meta-analysis. In total, individuals with 312A allele and 312AA genotype showed increased lung cancer risk (A vs. G: OR = 1.06, 95% CI: 1.00-1.12; AA vs. AG+GG: OR = 1.20, 95% CI: 1.06-1.36; AA vs. GG: OR = 1.19, 95% CI: 1.04-1.36). In Asians, individuals with 312AA genotype showed 6.15 fold and 6.20 fold increased lung cancer risk in recessive genetic model and homogenous contrast respectively (AA vs. AG+GG: OR = 7.15, 95% CI: 1.90-26.94; AA vs. GG: OR = 7.20, 95% CI: 1.91-27.15). In Caucasians, individuals with 312AA genotype showed a 15% increased lung cancer risk (OR = 1.15, 95% CI: 1.01-1.31).

CONCLUSIONXPD 312A allele is risk allele for lung cancer. Individuals with AA genotype have higher risk of lung cancer, especially in Asians.

Genotype ; Humans ; Lung Neoplasms ; etiology ; genetics ; Odds Ratio ; Polymorphism, Genetic ; Xeroderma Pigmentosum Group D Protein ; genetics

This study was aimed to explore the relationship between the single nucleotide polymorphisms of XPD (G23591A, A35931C) and individual susceptibility to non-Hodgkin's lymphomas (NHL) in Shandong populations. XPD gene polymorphism in 309 cases of NHL and 305 healthy controls were detected using PCR-restriction fragment length polymorphism assay in a case-control molecular epidemiology study. The association between gene polymorphism and the risk of NHL were examined through comparing odds ratio (OR) and 95% confidence interval (CI) between two groups. The results showed that no significant association between the XPD (G23591A, A35931C) polymorphism and the risk of whole NHL was shown at first. In the further analysis, all NHL cases were divided into four groups: follicular lymphoma (FL) group, diffuse large B-cell lymphoma (DLBCL) group, T-cell lymphoma group and other B-cell lymphoma group. Frequencies of XPD 23591GA + AA genotypes were 16.3%, 18.0%, 10.5% and 18.4% in each subgroup respectively, while 12.5% in control. Individuals carrying GA + AA genotype had 1.43, 1.58, 0.89 and 1.50-fold risk of NHL sub groups as much as GG genotype, but no statistically significant difference between subgroups and control was found (p>0.05); frequencies of XPD 35931AC + CC genotypes were 15.2%, 15.8%, 18.4% and 12.5% in each subgroup, while 11.5% in control. Individuals carrying AC + CC genotype had 1.41, 1.48, 1.75 and 1.12-fold risk of NHL subgroup as much as AA genotype, but there were also no statistically significant difference between each subgroup and control (p>0.05). It is concluded that the gene polymorphism of XPD (G23591A, G935931C) does not associate with the risk of developing NHL in Shandong populations.
Adult ; DNA Repair ; Female ; Humans ; Lymphoma, Non-Hodgkin ; genetics ; Male ; Middle Aged ; Point Mutation ; Polymorphism, Genetic ; Risk Factors ; Xeroderma Pigmentosum Group D Protein ; genetics ; Young Adult

OBJECTIVETo explore the association between polymorphisms in the DNA repair gene, xeroderma pigmentosum group D (XPD), and development of hepatocellular carcinoma (HCC) in the Chinese population by performing a systematic review of the previously published clinical data.

METHODA comprehensive literature search of the BIOSIS Previews and PubMed databases was carried out to identify all case-control studies of XPD polymorphisms and HCC risk. Meta-analysis was conducted to calculate the pooled odds ratios (ORs) with 95% confidence intervals (CIs) of developing HCC for carriers of the various XPD polymorphisms.

RESULTSSix case-control studies were selected for this meta-analysis, and comprised a total of 3424 HCC cases and 3636 controls. The pooled ORs (95% CIs) of XPD codon 751 and 312 allelomorphs were 1.25 (0.70 to 2.24) and 0.85 (0.58 to 1.25), respectively. Compared with the XPD wild-type homozygote Lys/Lys genotype of codon 751, the pooled OR (95% CI) of Lys/G1n + Gln/Gln genotypes for HCC risk was 1.31 (0.71 to 2.42). Compared with the XPD wild-type homozygote Asp/Asp genotype of codon 312, the pooled OR (95% CI) of Asp/Asn + Asn/Asn genotypes for HCC risk was 1.19 (0.73 to 1.95).

CONCLUSIONPolymorphisms in the XPD codons 751 and 312 are not associated with HCC risk in the Chinese population.

Carcinoma, Hepatocellular ; genetics ; Codon ; genetics ; DNA Repair ; Genetic Predisposition to Disease ; Humans ; Liver Neoplasms ; genetics ; Polymorphism, Genetic ; Xeroderma Pigmentosum Group D Protein ; genetics

OBJECTIVETo study the association between polymorphism of DNA repair gene xeroderma pigmentosum G (XPG) Asp1104His and the risks of developing laryngeal and hypopharyngeal carcinomas.

METHODSTotally 175 patients with laryngeal or hypopharyngeal carcinoma and 525 cancer-free controls were genotyped for the polymorphism by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The odds ratio (OR) and 95% confidence interval (CI) were calculated using unconditional logistic regression model.

RESULTSCompared with those having the Asp/Asp genotype, patients having the XPG 1104Asp/His genotype had a higher risk for laryngeal carcinoma (OR = 2.46, 95% CI = 1.15-5.24, P < 0.05), but not for hypopharyngeal carcinoma (OR = 1.36, 95% CI = 0.87-2.12, P > 0.05). In addition, the XPG 1104Asp/His genotype appeared to be associated with well differentiated squamous cell carcinoma in both larynx and hypopharynx (OR = 1.88, 95% CI = 1.05-3.40, P < 0.05 ).

CONCLUSIONThe XPG Asp1104His polymorphism may play a role in the development of laryngeal and hypopharyngeal carcinomas.

Case-Control Studies ; Female ; Genetic Predisposition to Disease ; Genotype ; Humans ; Hypopharyngeal Neoplasms ; genetics ; pathology ; Laryngeal Neoplasms ; genetics ; pathology ; Male ; Polymorphism, Genetic ; Xeroderma Pigmentosum Group D Protein ; genetics

OBJECTIVETo explore the influence of the DNA repair gene ERCC2 single nucleotide polymorphisms (SNPs) rs13181, rs1618536, and rs1799793 on male idiopathic infertility in Ningxia, China.

METHODSUsing MassArray, we conducted a case-control study and genotyped three ERCC2 SNPs rs13181, rs1618536, and rs1799793 for 351 males (aged 31.0 +/- 4.2 years) with idiopathic infertility and another 327 normal fertile men (aged 33.0 +/- 5.9 years) as controls.

RESULTSThe ERCC2 AnyG-anyA-anyA genotypes were significantly associated with an increased risk of idiopathic infertility (OR 0.414, 95% CI 0.176 - 0.970), while the three single ERCC2 SNPs rs13181, rs1618536, and rs1799793 showed no significant differences between the cases and controls (P > 0.05).

CONCLUSIONThe ERCC2 SNPs rs13181, rs1618536, and rs1799793 play a role of interaction in male idiopathic infertility in Ningxia, contributing to the risk of the disease.

Adult ; Case-Control Studies ; China ; DNA Repair ; Genotype ; Humans ; Infertility, Male ; genetics ; Male ; Polymorphism, Single Nucleotide ; Xeroderma Pigmentosum Group D Protein ; genetics

BRCA1 Protein ; genetics ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; Designer Drugs ; therapeutic use ; Humans ; Lung Neoplasms ; drug therapy ; Precision Medicine ; methods ; Tubulin ; genetics ; Xeroderma Pigmentosum Group D Protein ; genetics

OBJECTIVE: To analyze the association between genetic polymorphisms of DNA repair genes of XPD (751 Lys/Gln), XPC (PAT)and susceptibility to laryngeal carcinoma. To explore the effect between DNA repair genes of XPD (751 Lys/Gln), XPC (PAT) and carcinogenesis of LSCC(laryngeal squamous cell carcinoma). METHOD: A case-control study was conducted involving 233 LSCC patients and 102 healthy controls to investigate the association between polymorphisms of XPD(751 Lys/Gln), XPC (PAT) and LSCC. All blood samples of the Han people from the Guang Dong Zone was analysze with methods of PCR, PCR-RFLP, ASA and the technique of checking DNA sequencing with sequenator. We explored the association between polymorphisms and the clinical pathologic characteristic of LSCC. The data was compute with SPSS13.0. Odds Ratios (ORs) with 95% CI for relevancy intensity were calculated using binary logistic regression analysis. REULT: There is no difference of the frequency of XPC-PAT and XPD (751 Lys/Gln) genotype between in LSCC and in healthy contradistinguish (P > 0.05). CONCLUSION There may be no association between the susceptibility to laryngeal carcinoma and the genotype of XPC-PAT and XPD (751 Lys/Gln).
Carcinoma, Squamous Cell ; genetics ; Case-Control Studies ; DNA Repair ; genetics ; DNA-Binding Proteins ; genetics ; Female ; Genotype ; Humans ; Laryngeal Neoplasms ; genetics ; Male ; Polymorphism, Genetic ; Sequence Analysis, DNA ; Xeroderma Pigmentosum Group D Protein ; genetics

OBJECTIVETo confirm the enhancing effect of excision repair cross complementing rodent repair deficiency gene 2 (ERCC2) on alkylating agents resistance.

METHODSThe authors constructed a pcDNA3-ERCC2 plasmid. The pcDNA3-ERCC2 was transfected into a selected ERCC2 negative human glioma cell line, SKMG-4, using liposome-mediated transfection. After G418 selection, a stable transfected cell line was obtained and tested for cytotoxicity of several alkylating agents.

RESULTSThe stable transfectant was obtained and confirmed by RT-PCR as well as Western blot analysis to be strongly expressing ERCC2 at both mRNA and protein levels. The IC(90) ( micro mol/L) of two alkylating agents, cisplatin and melphalan, increased from 1.0 to 1.75 (75%) and 5.6 to 9.0 (61%), respectively, compared with control cell line.

CONCLUSIONThe present data provided evidences and confirmed the authors' previous results that ERCC2 contributes, at least partially, to alkylating agent resistance in human glioma cell line.

Antineoplastic Agents, Alkylating ; pharmacology ; Cisplatin ; pharmacology ; DNA Helicases ; DNA-Binding Proteins ; Drug Resistance, Neoplasm ; genetics ; Glioma ; Humans ; Melphalan ; pharmacology ; Proteins ; genetics ; Transcription Factors ; Transfection ; Tumor Cells, Cultured ; Xeroderma Pigmentosum Group D Protein