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.

Highlights

  • Colorectal cancer remains a significant cause of mortality worldwide

  • Previous studies reported that Enhancer of zeste homolog 2 (EZH2) is a tumorigenic gene that correlates with cancer progression and a poor prognosis [4, 29]

  • A correlation was not observed between overall survival (OS) and EZH2 expression levels in unresectable patients

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Summary

Introduction

Colorectal cancer remains a significant cause of mortality worldwide. Despite an earlier diagnosis and advances in available treatments, many colorectal cancers remain incurable [1, 2]. Molecular profiling will assist in the development of personalized treatment strategies [3]. Enhancer of zeste homolog 2 (EZH2), a component of the oncogene polycomb repressive complex 2, exhibits histone methyltransferase activity and induces the methylation of lysine residues in histone H3. EZH2 was previously shown to be overexpressed in cancers, and EZH2 expression levels a 2014 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. Cancer Medicine published by John Wiley & Sons Ltd

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