Downregulation of tumor suppressor gene ribonuclease T2 and gametogenetin binding protein 2 is associated with drug resistance in ovarian cancer.

Abstract

Ribonuclease T2 (RNASET2) and gametogenetin binding protein 2 (GGNBP2) are tumor suppressor genes whose expression is downregulated in ovarian and other types of cancer. However, whether the proteins encoded by these genes are associated with drug resistance has rarely been studied. Using real-time quantitative polymerase chain reaction, in the present study we showed that RNASET2 and GGNBP2 mRNA levels were significantly lower in A2780-CBP (carboplatin-resistant) and A2780-DDP (cisplatin-resistant) ovarian cancer cells than in the parental A2780 cells and were downregulated in drug-resistant ovarian cancer tissues compared with their drug-sensitive counterparts. These findings were consistent with the expression profiles determined from microarray data retrieved from the Gene Expression Omnibus Profiles database. Accordingly, we hypothesized that the downregulation of RNASET2 and GGNBP2 is involved in the development of drug resistance in ovarian cancer. A comprehensive bioinformatics analysis of the two genes was therefore conducted, including gene/protein-gene/protein interactions, biological process annotation, pathway enrichment of co-expressed genes and microRNA-mRNA analyses. The integrated results suggested that RNASET2 and GGNBP2 contributed to drug resistance in ovarian cancer, via direct or indirect interactions with a number of microRNAs, genes and proteins involved in a wide range of biological processes and pathways. The information provided in the present study provides insight for further investigations of the drug resistance-related functions of RNASET2 and GGNBP2.