Down-Regulation of microRNA-132 is Associated with Poor Prognosis of Colorectal Cancer.

Yukako Mokutani,Koji Munakata,Kohei Murata,Masaki Mori,Ichiro Takemasa,Taishi Hata,Hirofumi Yamamoto,Daisuke Okuzaki,Hidekazu Takahashi,Yuichiro Doki,Junichi Nishimura,Mamoru Uemura,Tsunekazu Mizushima,Naotsugu Haraguchi

doi:10.1245/s10434-016-5133-3

Yukako Mokutani, Koji Munakata + Show 12 more

Open Access

https://doi.org/10.1245/s10434-016-5133-3

Copy DOI

Abstract

BackgroundGiven the role of microRNA in colorectal cancer (CRC) progression, we explored the association between microRNA (miRNA) expression and CRC-related prognosis.Methods Three types of tissue samples (primary CRC lesions without liver metastasis, primary lesions with liver metastasis, and liver metastatic tissues) were used for miRNA profiling to identify differentially expressed miRNA. Quantitative real-time PCR was used to examine miRNA expression in CRC cells and in tumor tissues.Results MiR-132 was significantly down-regulated in primary CRC tissues with liver metastasis and liver metastatic lesions compared to primary lesions without liver metastasis. Multivariate analysis for overall survival indicated that low miR-132 expression was an independent prognostic factor for CRC patients (overall survival P = 0.040, disease-free survival P = 0.015). Ectopic expression of miR-132 significantly inhibited cell proliferation and cell invasion. The luciferase reporter assay revealed that anoctamin 1 (ANO1) was a direct target of miR-132. Kaplan–Meier survival curves showed that high ANO1 expression was a significant prognostic factor for overall survival of patients with CRC (P = 0.0344).ConclusionsDown-regulation of miR-132 is associated with poor prognosis in CRC. ANO1 could be one of the crucial targets of miR-132 in CRC.Electronic supplementary materialThe online version of this article (doi:10.1245/s10434-016-5133-3) contains supplementary material, which is available to authorized users.

Highlights

Given the role of microRNA in colorectal cancer (CRC) progression, we explored the association between microRNA expression and CRC-related prognosis
To explore the possible role of Micro RNAs (miRNAs) in CRC, miRNA expression was profiled in the testing cohort, which consisted of primary CRC tumor tissue from patients without liver metastasis (n = 16), tumor tissue from patients with liver metastasis (n = 12), and liver metastatic lesions (n = 8)
We found that a tumor suppressor miR-132 expression was significantly lower in CRC liver metastatic lesions than in primary CRC lesions without liver metastasis (Fig. 1a).[9]

Summary

Introduction

Given the role of microRNA in colorectal cancer (CRC) progression, we explored the association between microRNA (miRNA) expression and CRC-related prognosis. Three types of tissue samples (primary CRC lesions without liver metastasis, primary lesions with liver metastasis, and liver metastatic tissues) were used for miRNA profiling to identify differentially expressed miRNA. Quantitative real-time PCR was used to examine miRNA expression in CRC cells and in tumor tissues. MiR-132 was significantly down-regulated in primary CRC tissues with liver metastasis and liver metastatic lesions compared to primary lesions without liver metastasis. Multivariate analysis for overall survival indicated that low miR-132 expression was an independent prognostic factor for CRC patients (overall survival P = 0.040, disease-free survival P = 0.015). Ectopic expression of miR-132 significantly inhibited cell proliferation and cell invasion.

Methods

Results

Conclusion