Up-regulation of NEK2 by MicroRNA-128 methylation is associated with poor prognosis in colorectal cancer

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

Research output: Contribution to journalArticle

50 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)205-212
Number of pages8
JournalAnnals of Surgical Oncology
Volume21
Issue number1
DOIs
Publication statusPublished - Jan 1 2014

Fingerprint

MicroRNAs
Methylation
Colorectal Neoplasms
Up-Regulation
NIMA-Related Kinases
Neoplasms
Centrosome
DNA Methylation
Cell Cycle Checkpoints
Epigenomics
Cell Division
Reverse Transcription
Real-Time Polymerase Chain Reaction
Multivariate Analysis
Cell Proliferation
Recurrence
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Surgery
  • Oncology

Cite this

Up-regulation of NEK2 by MicroRNA-128 methylation is associated with poor prognosis in colorectal cancer. / Takahashi, Yusuke; Iwaya, Takeshi; Sawada, Genta; Kurashige, Junji; Matsumura, Tae; Uchi, Ryutaro; Ueo, Hiroki; Takano, Yuki; Eguchi, Hidetoshi; Sudo, Tomoya; Sugimachi, Keishi; Yamamoto, Hirofumi; Doki, Yuichiro; Mori, Masaki; Mimori, Koshi.

In: Annals of Surgical Oncology, Vol. 21, No. 1, 01.01.2014, p. 205-212.

Research output: Contribution to journalArticle

Takahashi, Y, Iwaya, T, Sawada, G, Kurashige, J, Matsumura, T, Uchi, R, Ueo, H, Takano, Y, Eguchi, H, Sudo, T, Sugimachi, K, Yamamoto, H, Doki, Y, Mori, M & Mimori, K 2014, 'Up-regulation of NEK2 by MicroRNA-128 methylation is associated with poor prognosis in colorectal cancer', Annals of Surgical Oncology, vol. 21, no. 1, pp. 205-212. https://doi.org/10.1245/s10434-013-3264-3
Takahashi, Yusuke ; Iwaya, Takeshi ; Sawada, Genta ; Kurashige, Junji ; Matsumura, Tae ; Uchi, Ryutaro ; Ueo, Hiroki ; Takano, Yuki ; Eguchi, Hidetoshi ; Sudo, Tomoya ; Sugimachi, Keishi ; Yamamoto, Hirofumi ; Doki, Yuichiro ; Mori, Masaki ; Mimori, Koshi. / Up-regulation of NEK2 by MicroRNA-128 methylation is associated with poor prognosis in colorectal cancer. In: Annals of Surgical Oncology. 2014 ; Vol. 21, No. 1. pp. 205-212.
@article{4fcfc18dd56b457cb4cdcbf2ceecb3c7,
title = "Up-regulation of NEK2 by MicroRNA-128 methylation is associated with poor prognosis in colorectal cancer",
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.",
author = "Yusuke Takahashi and Takeshi Iwaya and Genta Sawada and Junji Kurashige and Tae Matsumura and Ryutaro Uchi and Hiroki Ueo and Yuki Takano and Hidetoshi Eguchi and Tomoya Sudo and Keishi Sugimachi and Hirofumi Yamamoto and Yuichiro Doki and Masaki Mori and Koshi Mimori",
year = "2014",
month = "1",
day = "1",
doi = "10.1245/s10434-013-3264-3",
language = "English",
volume = "21",
pages = "205--212",
journal = "Annals of Surgical Oncology",
issn = "1068-9265",
publisher = "Springer New York",
number = "1",

}

TY - JOUR

T1 - Up-regulation of NEK2 by MicroRNA-128 methylation is associated with poor prognosis in colorectal cancer

AU - Takahashi, Yusuke

AU - Iwaya, Takeshi

AU - Sawada, Genta

AU - Kurashige, Junji

AU - Matsumura, Tae

AU - Uchi, Ryutaro

AU - Ueo, Hiroki

AU - Takano, Yuki

AU - Eguchi, Hidetoshi

AU - Sudo, Tomoya

AU - Sugimachi, Keishi

AU - Yamamoto, Hirofumi

AU - Doki, Yuichiro

AU - Mori, Masaki

AU - Mimori, Koshi

PY - 2014/1/1

Y1 - 2014/1/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84891737881&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84891737881&partnerID=8YFLogxK

U2 - 10.1245/s10434-013-3264-3

DO - 10.1245/s10434-013-3264-3

M3 - Article

C2 - 24046120

AN - SCOPUS:84891737881

VL - 21

SP - 205

EP - 212

JO - Annals of Surgical Oncology

JF - Annals of Surgical Oncology

SN - 1068-9265

IS - 1

ER -