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01-01-2014 | Colorectal Cancer

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

Authors: Yusuke Takahashi, MD, Takeshi Iwaya, MD, PhD, Genta Sawada, MD, Junji Kurashige, MD, PhD, Tae Matsumura, MD, Ryutaro Uchi, MD, Hiroki Ueo, MD, Yuki Takano, MD, Hidetoshi Eguchi, MD, PhD, Tomoya Sudo, MD, PhD, Keishi Sugimachi, MD, PhD, Hirofumi Yamamoto, MD, PhD, Yuichiro Doki, MD, PhD, Masaki Mori, MD, PhD, FACS, Koshi Mimori, MD, PhD

Published in: Annals of Surgical Oncology | Issue 1/2014

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.

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Title: Up-regulation of NEK2 by MicroRNA-128 Methylation is Associated with Poor Prognosis in Colorectal Cancer
Authors: Yusuke Takahashi, MD
Takeshi Iwaya, MD, PhD
Genta Sawada, MD
Junji Kurashige, MD, PhD
Tae Matsumura, MD
Ryutaro Uchi, MD
Hiroki Ueo, MD
Yuki Takano, MD
Hidetoshi Eguchi, MD, PhD
Tomoya Sudo, MD, PhD
Keishi Sugimachi, MD, PhD
Hirofumi Yamamoto, MD, PhD
Yuichiro Doki, MD, PhD
Masaki Mori, MD, PhD, FACS
Koshi Mimori, MD, PhD
Publication date: 01-01-2014
Publisher: Springer US
Published in: Annals of Surgical Oncology / Issue 1/2014
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI: https://doi.org/10.1245/s10434-013-3264-3

Keynote webinar | Spotlight on medication adherence

Springer Medicine

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

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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