Downregulation of NEK11 is associated with drug resistance in ovarian cancer.

Abstract

NEKs [NIMA (never in mitosis gene A)-related expressed kinase] are involved in ovarian cancer development and progression, while their association with drug resistance is limited, especially NEK11, and its relationship with drug resistance has never been reported. In this study, on the basis of comprehensive bioinformatic analyses, including mRNA expression according to microarray data, protein/gene interaction, protein-small molecule interaction, annotation of biological process and microRNA-mRNA interaction analysis, we revealed that the NEK11 mRNA was significantly downregulated in 586 cases of ovarian serous cystadenocarcinomas and cisplatin-resistant A2780 ovarian cancer cells, and interacted with 22 proteins and 4 small molecules which all were contributed to drug resistance in ovarian cancer. Furthermore, seven cell cycle-related biological processes were annotated with NEK11, drug resistance and ovarian cancer, suggesting that NEK11 potentially was involved in the drug resistance in ovarian cancer via its regulatory roles in the cell cycle. In addition, among the eight microRNAs predicted to be most strongly targeting NEK11, the majority were involved in drug resistance in ovarian and other cancers. All those results provide a very strong possibility that the notable downregulation of NEK11 in cisplatin-resistant ovarian cancer cells was involved in drug resistance, via its interactions with drug resistance-related genes, proteins, small molecules, microRNAs and biological processes, particularly the cell cycle-related processes. To our knowledge, this is the first report of the association of NEK11 with drug resistance in cancer, and it would pave the way for further investigation of the drug resistance-related functions of this gene.