Disease relevance of ZNRD1

• Suppression of the cell proliferation in stomach cancer cells by the ZNRD1 gene [1].
• Thus, the expression of ZNRD1 in normal gastric tissues was significantly higher than that in gastric adenocarcinomas [2].
• Anti-ZNRD1 monoclonal antibody H6 was found to react with 38 (63%) of normal gastric tissues, and 51 (81%) of gastritis [2].
• In this study, we firstly characterized ZNRD1 expression in a wide spectrum of gastric diseases by immunohistochemistry and RT-PCR [2].
• Most of the known genes were the RCC-related genes previously unknown, including zinc ribbon domain-containing 1 protein (ZNRD1), pituitary tumor transforming gene1 (PTTG1) [3].

High impact information on ZNRD1

• A new zinc ribbon gene (ZNRD1) is cloned from the human MHC class I region [4].
• We also introduced the ZNRD1 gene into gastric cancer cells that do (SGC7901) and do not (AGS) express ZNRD1 endogenously [1].
• In this study, we constructed the siRNA eukaryotic expression vectors of ZNRD1 and transfected them into normal gastric epithelial cells (GES-1) [1].
• ZNRD1 mediates resistance of gastric cancer cells to methotrexate by regulation of IMPDH2 and Bcl-2 [5].
• We previously showed that downregulation of a transcription-associated gene (ZNRD1) could reverse the resistant phenotype of gastric cancer cells through regulation of the transcription of multidrug resistance gene 1 (MDR1) [5].

Chemical compound and disease context of ZNRD1

• ZNRD1 antisense nucleic acid transfection sensitized drug resistant gastric cancer cells to VCR, increased ADM accumulation and inhibited the cells proliferation [6].

Biological context of ZNRD1

• ZNRD1 was genetically overexpressed in SGC7901 cells by gene transfection [7].
• Upregulation of ZNRD1 protein in SGC7901/VCR cells was confirmed by Western blot and immunocytochmical staining [7].
• Overexpression of ZNRD1 promotes multidrug-resistant phenotype of gastric cancer cells through upregulation of P-glycoprotein [7].
• ZNRD1 gene suppresses cell proliferation through cell cycle arrest in G1 phase [2].
• Additionally, inhibition of ZNRD1 could suppress adriamycin-induced apoptosis and significantly downregulate the expression of Bcl-2, but it did not alter the expression of the glutathione-S-transferase, or intracellular glutathione content [5].

Anatomical context of ZNRD1

• ZNRD1, a new zinc ribbon gene, has been previously identified as an upregulated gene in a multidrug-resistant gastric cancer cell line SGC7901/VCR comparing to its parental cell SGC7901 by subtractive hybridization and RT-PCR [7].
• Up-regulation of ZNRD1 expression could confer resistance of both P-glycoprotein (P-gp)-related and P-gp-nonrelated drugs on HL-60 cells and suppress Adriamycin-induced apoptosis accompanied by decreased accumulation and increased releasing amount of Adriamycin [8].

Associations of ZNRD1 with chemical compounds

• The antisense nucleic acid for ZNRD1 could enhance adriamycin accumulation in SGC7901/VCR cells and sensitize SGC7901/VCR cells to vincristine [7].
• Verapamil, an inhibitor for P-gp, could reverse the effects of ZNRD1 on drug sensitivity and drug accumulation in SGC7901 cells to a great extent [7].
• In vitro and in vivo drug sensitivity analyses revealed that inhibition of ZNRD1 and IMPDH2 activity sensitized SGC7901/VCR cells to methotrexate [5].
• FACS also suggested intracellular ADM accumulation increased 2fold in SGC7901/VCR cells after transfected with antisense ZNRD1 [6].
• Down-regulation of ZNRD1 significantly enhanced the sensitivity of SGC7901/VCR cells to vincristine, adriamycin and etoposide, but not to 5-fluorouracil and cisplatin [9].

Other interactions of ZNRD1

• The present study aims to explore the role of ZNRD1 in multidrug resistance in gastric cancer cells [7].
• Immunohistochemical and Western blot analysis for PTTG1 and ZNRD1 revealed increased protein level in RCC [3].

Analytical, diagnostic and therapeutic context of ZNRD1

• Western blot and Northern blot revealed that overexpression of ZNRD1 could upregulate P-gp at both protein and mRNA levels [7].
• METHODS: Amplification of sequences encoding ZNRD1 from SGC7901/VCR cDNA by PCR [6].
• Taken together, the findings suggest that ZNRD1 could act as a modulator of methotrexate chemotherapy in gastric cancer cells through the regulation of IMPDH2 and Bcl-2 [5].

References