NEK2 Promotes Hepatoma Metastasis and Serves as Biomarker for High Recurrence Risk after Hepatic Resection

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

Resumen

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.

Palabras clave: Hepatocellular carcinoma cancer progression cell cycle invasion hepatitis virus.

2018-09-24   |   435 visitas   |   Evalua este artículo 0 valoraciones

Vol. 17 Núm.5. Septiembre-Octubre 2018 Pags. 843-856 Ann Hepatol 2018; 17(5)