Annals of Surgical Oncology

, Volume 21, Issue 1, pp 205–212

Up-regulation of NEK2 by MicroRNA-128 Methylation is Associated with Poor Prognosis in Colorectal Cancer

Authors

  • Yusuke Takahashi
    • Department of Surgery, Beppu HospitalKyushu University
    • Department of Gastroenterological Surgery, Graduate School of MedicineOsaka University
  • Takeshi Iwaya
    • Department of Surgery, Beppu HospitalKyushu University
  • Genta Sawada
    • Department of Surgery, Beppu HospitalKyushu University
    • Department of Gastroenterological Surgery, Graduate School of MedicineOsaka University
  • Junji Kurashige
    • Department of Surgery, Beppu HospitalKyushu University
  • Tae Matsumura
    • Department of Surgery, Beppu HospitalKyushu University
    • Department of Gastroenterological Surgery, Graduate School of MedicineOsaka University
  • Ryutaro Uchi
    • Department of Surgery, Beppu HospitalKyushu University
  • Hiroki Ueo
    • Department of Surgery, Beppu HospitalKyushu University
  • Yuki Takano
    • Department of Surgery, Beppu HospitalKyushu University
  • Hidetoshi Eguchi
    • Department of Surgery, Beppu HospitalKyushu University
  • Tomoya Sudo
    • Department of Surgery, Beppu HospitalKyushu University
  • Keishi Sugimachi
    • Department of Surgery, Beppu HospitalKyushu University
  • Hirofumi Yamamoto
    • Department of Gastroenterological Surgery, Graduate School of MedicineOsaka University
  • Yuichiro Doki
    • Department of Gastroenterological Surgery, Graduate School of MedicineOsaka University
  • Masaki Mori
    • Department of Gastroenterological Surgery, Graduate School of MedicineOsaka University
    • Department of Surgery, Beppu HospitalKyushu University
Colorectal Cancer

DOI: 10.1245/s10434-013-3264-3

Cite this article as:
Takahashi, Y., Iwaya, T., Sawada, G. et al. Ann Surg Oncol (2014) 21: 205. doi:10.1245/s10434-013-3264-3

Abstract

Background

NIMA-related kinase 2 (NEK2), an enzyme involved in the development and progression of cancer, is abnormally expressed in a wide variety of human cancers, including colorectal cancer (CRC), and is known to have roles in cell division and mitotic regulation through centrosome splitting. We investigated the clinical significance of NEK2 in CRC. In particular, we examined miR-128 expression, which is thought to target NEK2.

Methods

We measured NEK2 mRNA and miR-128 levels in clinical samples by quantitative reverse transcription real-time PCR and analyzed the associations between NEK2 levels, miR-128 levels, clinicopathological factors, and prognoses. Furthermore, we performed in vitro assays using a pre-miR-128 precursor and conducted miR-128 methylation analyses.

Results

MiR-128 inhibited NEK2 expression and cancer cell proliferation via cell cycle arrest. Moreover, miR-128 was silenced by DNA methylation. Increased NEK2 expression was associated with serosal invasion, lymphatic invasion, and peritoneal dissemination. Patients with high NEK2 expression also had significantly poorer prognoses. Multivariate analysis indicated that high NEK2 expression was an independent prognostic factor for survival. Patients with high miR-128 expression had significantly lower NEK2 expression and lower recurrence rates than those with low miR-128 expression.

Conclusions

NEK2 may be an independent prognostic factor for CRC and was regulated by miR-128, a microRNA that was subjected to epigenetic regulation. Thus, this miR-128/NEK2 pathway may be a prospective therapeutic target for patients with CRC.

Copyright information

© Society of Surgical Oncology 2013