Low expression levels of microRNA‐124‐5p correlated with poor prognosis in colorectal cancer via targeting of SMC4

Cancer Medicine

Takafumi Jinushi³  Yoshihiko Shibayama¹  Ichiro Kinoshita⁵  Satoshi Oizumi²  Masahisa Jinushi⁶  Tadahiro Aota⁴  Toshiyuki Takahashi⁴  Shoichi Horita⁴  Hirotoshi Dosaka-Akita⁵ 

[1] Graduate School of Pharmaceutical Sciences, Education Research Center for Clinical Pharmacy, Hokkaido University, Sapporo, Japan;Graduate School of Medicine, First Department of Medicine, Hokkaido University, Sapporo, Japan;Graduate School of Pharmaceutical Sciences, Clinical Pharmaceutics and Therapeutics, Hokkaido University, Sapporo, Japan;Hokkaido Gastroenterology Hospital, Sapporo, Japan;Graduate School of Medicine, Department of Medical Oncology, Hokkaido University, Sapporo, Japan;Research Center for Infection-Associated Cancer, Institute for Genetic Medicine, Sapporo, Japan

关键词: Colorectal cancer;    EZH2;    MFGE8;    miR‐124‐5p;    miR‐26a;    SMC4;   

DOI  :  10.1002/cam4.309

来源: Wiley

【 摘 要 】

Abstract

A component of polycomb repressor complex 2, enhancer of zeste homolog 2 (EZH2), plays an important role in tumor malignancy and metastasis, while milk fat globule-epidermal growth factor-factor 8 (MFGE8) plays a key role in tumor progression and prognosis. MicroRNAs (miRs) are also critically involved in various physiological and pathological processes. We here evaluated the relationship between overall survival (OS) in colorectal cancer patients and the expression of onco-miRs and miRs, which may target EZH2 and MFGE8. Plasma and formalin-fixed paraffin-embedded (FFPE) samples were obtained from 71 colorectal cancer patients. The expression levels of miRs complementary to EZH2 and MFGE8 mRNA and cancer malignancies were evaluated. The miRs analyzed were as follows: miR-16, miR-21, miR-26a, miR-34a, miR-98, miR-101-3p, miR-101-5p, miR-124-5p (also known as miR-124*), miR-126-3p, miR-126-5p, miR-210, miR-217, and miR-630. The plasma expression levels of MFGE8 in completely resected patients were significantly lower than those in unresectable patients. Lower miR-26a expression levels were correlated with a higher probability of OS. Higher miR-124-5p expression levels in plasma and FFPE samples were correlated with a higher probability of OS. The transfection of mimic miR-124-5p into WiDr and COLO201 cells inhibited the expression of structural maintenance of chromosomes 4 (SMC4) mRNA. Our results indicate that miR-124-5p may target the tumorigenesis gene, SMC4, which suggests that expression levels of miR-124-5p in plasma and FFPE samples; therefore, the expression of MFGE8, miR-26a, and miR-124-5p in plasma may be used as biomarkers to determine the prognosis of colorectal cancer patients.

【 授权许可】

CC BY   
© 2014 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.