Upregulation of NEK2 is associated with drug resistance in ovarian cancer

Liu, Xia; Gao, Yanning; Lü, Yi; Zhang, Jian; Li, Li; Yin, Fuqiang

doi:10.3892/or.2013.2910

Cited by 71 publications

(63 citation statements)

References 82 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Using the comprehensive bioinformatics analyses, Yin et al (10) performed an integrated analysis of tumor suppressor genes with drug resistance in ovarian cancer, and two genes CCL21 and SPARCL1 associated with drug resistance were identified (85). Using similar bioinformatics analysis, upregulation of NEK2 was identified to be associated with drug resistance in ovarian cancer (86), and upregulation of E2F3 was identified to be associated with poor prognosis in HCC (87). The association of HNF1B with drug resistance in ovarian and other cancers has yet to be reported.…”

Section: Discussionmentioning

confidence: 99%

Downregulation of HNF1 homeobox B is associated with drug resistance in ovarian cancer

Zhang²,

Gao

et al. 2014

Oncology Reports

Self Cite

View full text Add to dashboard Cite

Abstract. The expression of HNF1 homeobox B (HNF1B) is associated with cancer risk in several tumors, including ovarian cancer, and its decreased expression play roles in cancer development. However, the study of HNF1B and cancer is limited, and its association with drug resistance in cancer has never been reported. On the basis of array data retrieved from Oncomine and Gene Expression Omnibus (GEO) online database, we found that the mRNA expression of HNF1B in 586 ovarian serous cystadenocarcinomas and in platinum-resistant A2780 epithelial ovarian cancer cells was significantly decreased, indicating a potential role of HNF1B in drug resistance in ovarian cancer. Based on this finding, comprehensive bioinformatics analyses, including protein/ gene interaction, protein-small molecule/chemical interaction, biological process annotation, gene co-occurrence and pathway enrichment analysis and microRNA-mRNA interaction, were performed to illustrate the association of HNF1B with drug resistance in ovarian cancer. We found that among the proteins/ genes, small molecules/chemicals and microRNAs which directly interacted with HNF1B, the majority was associated with drug resistance in cancer, particularly in ovarian cancer. Biological process annotation revealed that HNF1B closely related to 24 biological processes which were all notably associated with ovarian cancer and drug resistance. These results indicated that the downregulation of HNF1B may contribute to drug resistance in ovarian cancer, via its direct interactions with these drug resistance-related proteins/genes, small molecules/chemicals and microRNAs, and via its regulations on the drug resistance-related biological processes. Pathway enrichment analysis of 36 genes which co-occurred with HNF1B, ovarian cancer and drug resistance indicated that the HNF1B may perform its drug resistance-related functions through 4 pathways including ErbB signaling, focal adhesion, apoptosis and p53 signaling. Collectively, in this study, we illustrated for the first time that HNF1B may contribute to drug resistance in ovarian cancer, potentially through the 4 pathways. The present study may pave the way for further investigation of the drug resistance-related functions of HNF1B in ovarian cancer.

show abstract

Section: Discussionmentioning

confidence: 99%

Downregulation of HNF1 homeobox B is associated with drug resistance in ovarian cancer

Zhang²,

Gao

et al. 2014

Oncology Reports

Self Cite

View full text Add to dashboard Cite

show abstract

“…For example, a comprehensive bioinformatics approach, including microarrays, motif analysis, protein/gene interaction, proteinchemical interaction, biological process annotation, pathway enrichment and mRNA-microRNA interactions, has been used to identify the association of dysregulated SPARCL1 and chemokine (C-C motif) ligand 21 (CCL21) (41), NIMArelated kinase 11 (NEK11) (95) and NIMA-related kinase 2 (NEK2) (96), and ribonuclease T2 (RNASET2) and gametogenetin binding protein 2 (GGNBP2) (97) with drug resistance in Table II. Top 10 microRNAs targeting TRPC1, as predicted by microRNA-mRNA interactions and their drug-resistance-related functions in cancer.…”

Section: Discussionmentioning

confidence: 99%

Downregulation of transient receptor potential cation channel, subfamily C, member 1 contributes to drug resistance and high histological grade in ovarian cancer

Liu

Zou

et al. 2015

International Journal of Oncology

Self Cite

View full text Add to dashboard Cite

Abstract. Transient receptor potential cation channel, subfamily C, member 1 (TRPC1) participates in many physiological functions but has also been implicated in cancer development. However, little is known about the role of TRPC1 in ovarian cancer (OC), including the drug resistance of these tumors. In the present study, a significant and consistent downregulation of TRPC1 in drug-resistant OC tissues/cells was determined using real-time quantitative polymerase chain reaction assays and the microarrays deposited in Oncomine and Gene Expression Omnibus (GEO) Profiles. Protein/geneprotein/gene and protein-chemical interactions indicated that TRPC1 interacts with 14 proteins/genes and 6 chemicals, all of which are involved in the regulation of drug resistance in OC. Biological process annotation of TRPC1, OC, and drug resistance indicated a role for TRPC1 in drug-resistance-related functions in OC, mainly via the cell cycle, gene expression and cell growth and cell death. Analysis of mRNA-microRNA interactions showed that 8 out of 11 major pathways enriched from 38 predominant microRNAs targeting TRPC1 were involved in the regulation of drug resistance in OC, and 8 out of these top 10 microRNAs were implicated in the drug resistance in ovarian and other cancers. In a clinical analysis using data obtained from The Cancer Genome Atlas project (TCGA) cohort on 341 OC patients, TRPC1 expression was found to differ significantly between grade 2 and grade 3 tumors, with low-level expression correlating with higher tumor grade. This is the first report to show a potential association between the downregulation of TRPC1 and both drug resistance and high histological tumor grade in OC. Our results provide the basis for further investigations of the drug-resistance-related functions of TRPC1 in OC and other forms of cancer.

show abstract

“…Moreover in ovarian cancer, Nek2 mRNA expression is upregulated, especially in drug-resistant cells. The bioinformatic analysis revealed that Nek2 may directly or indirectly interact with a number of genes, proteins, microRNAs associated with drug resistance in ovarian and other types of cancer (28). Aberrant Nek2 expression has also been found in other cancers, such as non-small cell lung cancer and malignant peripheral nerve sheath tumor (29,30).…”

Section: Introductionmentioning

confidence: 99%

Nek2A/SuFu feedback loop regulates Gli-mediated Hedgehog signaling pathway

Zhou

Huang

et al. 2016

International Journal of Oncology

View full text Add to dashboard Cite

Suppressor of Fused (SuFu), one of the most conserved components of the Hedgehog (Hh) signaling, binds Gli transcription factors and impedes activation of target gene expression in mammalian cells. Despite the central importance of SuFu in the Hh pathway, little is known about SuFu regulation. In a previous study, we identified NIMA-related expressed kinase 2A (Nek2A) as a SuFu-interacting protein. Here, we show that Nek2A stabilizes SuFu through impairing ubiquitin/proteasome degradation of SuFu. In addition, Nek2A negatively regulates target genes of Hh signaling as well as Gli2 transcriptional activity. In turn, inhibition of Hh signaling by GANT61 diminishes mRNA and protein levels of Nek2A, and Hh agonist promotes transcription of NEK2A gene. Chromatin immunoprecipitation assays revealed that Gli1 and Gli2 directly bind to the promoter regions of NEK2A gene and induced its transcription. Thus, we uncovered one of the mechanisms by which Nek2A acts as a modulator of the Hh signaling pathway in the context of a novel negative-feedback loop, which may offer new insights into Gli-mediated Hh signaling regulation in development and human diseases.

show abstract

Upregulation of NEK2 is associated with drug resistance in ovarian cancer

Cited by 71 publications

References 82 publications

Downregulation of HNF1 homeobox B is associated with drug resistance in ovarian cancer

Downregulation of HNF1 homeobox B is associated with drug resistance in ovarian cancer

Downregulation of transient receptor potential cation channel, subfamily C, member 1 contributes to drug resistance and high histological grade in ovarian cancer

Nek2A/SuFu feedback loop regulates Gli-mediated Hedgehog signaling pathway

Contact Info

Product

Resources

About