Upregulation of ZNRD1 Enhances Cisplatin Resistance in Human Esophageal Cancer Cells by Regulation of ERCC1 and Bcl-2

Abstract

Background/Aims: The precise mechanism of the zinc ribbon domain-containing-1 (ZNRD1) gene on cisplatin resistance remains unclear. The aim of this study is to identify the gene expression profile and explore the role of these genes in ZNRD1-induced cisplatin resistance in esophageal cancer cells. Methods: An expression vector with ZNRD1 was transfected into the EC109 cells, and then cDNA microarray analysis was performed to identify the gene expression profile. The sensitivity of transfected EC109 cells to cisplatin was evaluated using the MTT assay. RT-PCR and Western blots were performed to validate the differential expression of genes identified by cDNA microarray analysis. Results: We identified 16 genes with significantly different expression levels between the transfected and control cells. The tolerance of EC109 cells to cisplatin was significantly enhanced by the upregulation of ZNRD1. Furthermore, the expression of excision repair cross-complementing-1 (ERCC1) and B-cell lymphoma-2 (Bcl-2) was significantly upregulated. Conclusion: The ZNRD1 gene might be involved in the cisplatin resistance of EC109 cells by regulating the expression of ERCC1 and Bcl-2.

PRIC295, a Nuclear Receptor Coactivator, Identified from PPAR-Interacting Cofactor Complex

“…Zinc ribbon domain-containing 1 (ZNRD1) was also among the complex of PRIC295-interacting proteins. ZNRD1 has a role in regulating ERCC1 and Bcl-2 which are important in cancer progression though the mechanism by which it does this is presently unclear [85]. ZNRD1 also appears to have an influence in the progression of HIV infection [86].…”

Single nucleotide polymorphisms in ZNRD1-AS1 increase cancer risk in an Asian population

“…It catalyzes the transcription of DNA into RNA and is a potential therapeutic target for various diseases [16, 17]. Reduced ZNRD1 expression was observed in human gastric cancer [18, 19].…”

MicroRNA-induced drug resistance in gastric cancer

“…Moreover, they found that miR-508-5p directly targeted the 3 0 UTR of P-gp and ZNRD1, resulting in their repressed expression at protein and mRNA levels. Zinc ribbon domain-containing 1 (ZNRD1) is a MDRassociated gene whose overexpression has been reported in chemotherapeutic resistant cancer cells, and its knockdown could sensitize gastric cancer cells to various anticancer compounds [23,24]. In addition, ZNRD1 was also shown to be a modulator of Bcl-2 [23,25].…”

“…Zinc ribbon domain-containing 1 (ZNRD1) is a MDRassociated gene whose overexpression has been reported in chemotherapeutic resistant cancer cells, and its knockdown could sensitize gastric cancer cells to various anticancer compounds [23,24]. In addition, ZNRD1 was also shown to be a modulator of Bcl-2 [23,25]. Inhibition of P-gp and ZNRD1 expression abrogated the chemotherapeutic resistance induced by miR-508-5p silencing.…”