NEK2 promotes hepatoma metastasis and serves as biomarker for high recurrence risk after hepatic resection

Yu Ying Chang, Chia Jui Yen, Shih Huang Chan, Yi Wen Chou, Yun Ping Lee, Ching Yu Bao, Chien Jung Huang, Wenya Huang

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

Introduction and aim. Developing reliable biomarkers for hepatocellular carcinoma (HCC) patients who are at a high risk of recurrence after curative hepatic resection is very important for determining subsequent therapeutic strategies. We investigated the role of the cell cycle factor NIMA-related kinase 2 (NEK2) in HCC progression in hepatoma cells and post-surgery patients. Material and methods. The effects of NEK2 on proliferation, invasion and migration of hepatoma HuH7 and SK-Hep1 cells were evaluated. In a post-surgery HCC cohort (N = 97), the Nek2 induction levels in the tumors were examined with real-time RT-PCR analysis, and the results were analyzed for their correlations with recurrence. Results. NEK2 promoted G1 to S phase cell cycle progression by causing increases in cyclin D1 and AKT phosphorylation and decreases in the cyclin-dependent kinase inhibitor p27, indicating that NEK2 plays an important role during interphase in addition to its previously identified role in M phase. NEK2 also enhanced the proliferation, migration and invasion of hepatoma cells and regulated the expression of E-cadherin and MMP9. The Nek2 mRNA levels in the tumors were highly correlated with recurrence rates in the post-surgery HCC patients. Combined evaluation of the tumor AJCC stage and the Nek2 level can serve as a reliable method for predicting the relative risk of HCC recurrence in these patients. Conclusions. NEK2 plays a significant role in cell cycle progression in the inter-and M-phases. NEK2 enhances HCC metastasis and is correlated with recurrence and thus can potentially serve a promising high-risk biomarker for HCC.

Original languageEnglish
Pages (from-to)843-856
Number of pages14
JournalAnnals of Hepatology
Volume17
Issue number5
DOIs
Publication statusPublished - 2018 Sep 1

All Science Journal Classification (ASJC) codes

  • Hepatology

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