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
N1 - Funding Information:
ACKNOWLEDGMENT We thank T. Shimooka, K. Oda, M. Kasagi, and S. Kono for their technical assistance. This work was supported in part by the following grants and foundations: CREST, Japan Science and Technology Agency (JST), and the Funding Program for Next Generation World-Leading Researchers (LS094).
PY - 2014/1
Y1 - 2014/1
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.
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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 -