ArticleThe Journal of biological chemistry2015
The tumor suppressor pVHL down-regulates never-in-mitosis A-related kinase 8 via hypoxia-inducible factors to maintain cilia in human renal cancer cells.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 38 citations in OpenAlex.
- Recent advances in etiology and treatment of von Hippel-Lindau Disease (VHLD).Cancer metastasis reviews · 2026Review
- NEK8 kinase-mediated lactate increase impairs antitumor immunity decreasing radiotherapy sensitivity in colorectal cancer.Nature communications · 2026Article
- Primary cilia in cancer: structures, functions, mechanisms, and therapeutic implications.Cancer biology & medicine · 2025Review
- The NIMA-related kinase family and cancer.Frontiers in oncology · 2025Review
- Primary cilia-associated signalling in squamous cell carcinoma of head and neck region.Frontiers in oncology · 2024Review
- The genomic and transcriptomic landscape of advanced renal cell cancer for individualized treatment strategies.Scientific reports · 2023Article
- Never in mitosis gene A-related kinase-8 promotes proliferation, migration, invasion, and stemness of breast cancer cells via β-catenin signalling activation.Scientific reports · 2023Article
- In Mitosis You Are Not: The NIMA Family of Kinases inInternational journal of molecular sciences · 2022Review
- Analysis of the effect of NEKs on the prognosis of patients with non-small-cell lung carcinoma based on bioinformatics.Scientific reports · 2022Article
- Never-in-Mitosis A-Related Kinase 8 (NEK8) Regulates Adipogenesis, Glucose Homeostasis, and Obesity.Oxidative medicine and cellular longevity · 2022Article
- Article
- Functional roles of E3 ubiquitin ligases in gastric cancer.Oncology letters · 2020Review
- The pVHL neglected functions, a tale of hypoxia-dependent and -independent regulations in cancer.Open biology · 2020Review
- The primary cilium: Its role as a tumor suppressor organelle.Biochemical pharmacology · 2020Review
- Checking NEKs: Overcoming a Bottleneck in Human Diseases.Molecules (Basel, Switzerland) · 2020Review
- Ciliary Genes in Renal Cystic Diseases.Cells · 2020Review
- Primary Cilium in Cancer Hallmarks.International journal of molecular sciences · 2019Review
- The uremic toxin p-cresyl sulfate induces proliferation and migration of clear cell renal cell carcinoma via microRNA-21/ HIF-1α axis signals.Scientific reports · 2019Article
- Mixed signals from the cell's antennae: primary cilia in cancer.EMBO reports · 2018Review
- Never-in-mitosis A-related kinase 8, a novel target of von-Hippel-Lindau tumor suppressor protein, promotes gastric cancer cell proliferation.Oncology letters · 2018Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
NEK8 (never in mitosis gene A (NIMA)-related kinase 8) is involved in cytoskeleton, cilia, and DNA damage response/repair. Abnormal expression and/or dysfunction of NEK8 are related to cancer development and progression. However, the mechanisms that regulate NEK8 are not well declared. We demonstrated here that pVHL may be involved in regulating NEK8. We found that CAK-I cells with wild-type vhl expressed a lower level of NEK8 than the cells loss of vhl, such as 786-O, 769-P, and A-498 cells. Moreover, pVHL overexpression down-regulated the NEK8 protein in 786-O cells, whereas pVHL knockdown up-regulated NEK8 in CAK-I cells. In addition, we found that the positive hypoxia response elements (HREs) are located in the promoter of the nek8 sequence and hypoxia could induce nek8 expression in different cell types. Consistent with this, down-regulation of hypoxia-inducible factors α (HIF-1α or HIF-2α) by isoform-specific siRNA reduced the ability of hypoxia inducing nek8 expression. In vivo, NEK8 and HIF-1α expression were increased in kidneys of rats subjected to an experimental hypoxia model of ischemia and reperfusion. Furthermore, NEK8 siRNA transfection significantly blocked pVHL-knockdown-induced cilia disassembling, through impairing the pVHL-knockdown-up-regulated NEK8 expression. These results support that nek8 may be a novel hypoxia-inducible gene. In conclusion, our findings show that nek8 may be a new HIF target gene and pVHL can down-regulate NEK8 via HIFs to maintain the primary cilia structure in human renal cancer cells.
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