Never‑in‑mitosis A‑related kinase 8, a novel target of von‑Hippel‑Lindau tumor suppressor protein, promotes gastric cancer cell proliferation

Ding,Xiao‑Fei; Chen,Jie; Zhou,Jun; Chen,Guang; Wu,Ying‑Liang

doi:10.3892/ol.2018.9328

Never‑in‑mitosis A‑related kinase 8, a novel target of von‑Hippel‑Lindau tumor suppressor protein, promotes gastric cancer cell proliferation

Authors:
- Xiao‑Fei Ding
- Jie Chen
- Jun Zhou
- Guang Chen
- Ying‑Liang Wu
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Affiliations: Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, P.R. China, Laboratory for Biological Medicine, School of Medicine, Taizhou University, Taizhou, Zhejiang 318000, P.R. China, Institute of Tumor, Taizhou University, Taizhou, Zhejiang 318000, P.R. China
Published online on: August 20, 2018 https://doi.org/10.3892/ol.2018.9328
Pages: 5900-5906
Copyright: © Ding et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Previous research has revealed that the von‑Hippel‑Lindau tumor suppressor protein (pVHL) may downregulate never‑in‑mitosis A‑related kinase 8 (NEK8) via hypoxia‑inducible factor‑α (HIF‑α). The HIF‑independent functions of pVHL also serve an important role in its tumor‑suppressor action. In the present study, the association between pVHL and NEK8 was demonstrated in the human gastric cancer cell line, SGC‑7901, indicating a direct interaction of pVHL with NEK8. Subsequently, it was reported that MG‑132, a specific proteasome inhibitor, may attenuate pVHL overexpression‑induced reductions in NEK8 protein expression levels. In addition, the present study revealed that pVHL may stimulate the rapid degradation of NEK8 protein and promote its ubiquitination. The association between the expression profile of NEK8 and the survival status of patients with gastric cancer was analyzed from an online database. Kaplan‑Meier survival plots indicated that higher expression levels of NEK8 may lead to poor survival, as suggested by the transcriptomic data of 1,065 patients with gastric cancer. It was found that NEK8‑knockdown mediated by RNA interference inhibited SGC‑7901 and SNU‑1 proliferation, colony formation and migration in vitro, and tumor growth in vivo. Collectively, the present study proposed that NEK8 may be a novel target of pVHL as a ubiquitin E3 ligase, and may serve a role as a potential oncoprotein in human gastric cancer.

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