Exosome-encapsulated microRNAs as circulating biomarkers for colorectal cancer.

Zengfang Wang,Shushan Yan,Donghua Xu,Beicheng Sun,Bing Han,Fakai Wang,Jianjun Zhang,Shunyuan Gao,Xiaochen Wang

doi:10.18632/oncotarget.18557

Abstract

Currently available studies have suggested that a number of exosome-encapsulated microRNAs (miRNAs) are recognized as stable biomarkers for cancers. However, little is known about the effect of exosomal miRNAs on colorectal cancer (CRC). The aim of study is to identify specific miRNAs in serum exosomes, which may serve as potential diagnostic and prognostic biomarkers and therapeutic targets for CRC. Microarray analyses of miRNAs in serum exosomes from 3 primary CRC patients and 3 healthy controls were performed. Those differentially expressed exosome-encapsulated miRNAs were verified in exosome-enriched serum samples from 77 CRC patients and 20 healthy controls by quantitative real-time PCR (qRT-PCR). A total of 39 aberrantly expressed miRNAs in serum exosomes were identified by microarray analysis. After confirmation by qRT-PCR, we found that 5 exosome-encapsulated miRNAs (miR-638, miR-5787, miR-8075, miR-6869-5p and miR-548c-5p) were significantly down-regulated, while 2 exosome-encapsulated miRNAs (miR-486-5p and miR-3180-5p) were significantly up-regulated in serum. Decreased levels of miR-638 in serum exosomes were associated with increased risk of liver metastasis and later TNM stage of CRC. Networks analyses revealed that 5 aberrantly expressed miRNAs (miR-638, miR-5787, miR-8075, miR-6869-5p, and miR-548c-5p) might be involved in the process of glucose metabolism in CRC. The present study shows the specific serum profile of exosome-encapsulated miRNAs in CRC. Those specific miRNAs in serum exosomes may serve as disease biomarkers and novel therapeutic targets for CRC.

Highlights

Colorectal cancer (CRC) is a common digestive cancer and one of the major causes of cancer-related deaths worldwide [1, 2]
Little is known about the association between exosomal miRNAs and colorectal cancer (CRC). We performed this microarray-based profiling of exosomal miRNAs in serum from CRC patients to demonstrate the underlying molecular networks involved in CRC development and progression, which may serve as disease biomarkers and novel therapeutic targets
There were a total of 39 aberrantly expressed miRNAs in serum exosomes from patients with CRC were identified by microarray analysis

Summary

INTRODUCTION

Colorectal cancer (CRC) is a common digestive cancer and one of the major causes of cancer-related deaths worldwide [1, 2]. Accumulating evidence has suggested that aberrantly expressed circulating noncoding RNAs, such as microRNAs (miRNAs), long noncoding RNAs (lncRNAs) and circular RNAs, can regulate the complicated process of cell proliferation, apoptosis and angiogenesis, and contribute to tumorigenesis and tumor progression [7,8,9,10]. These noncoding RNAs may be valuable noninvasive tools that can be used as diagnostic and prognostic biomarkers and therapeutic targets for cancer. We performed this microarray-based profiling of exosomal miRNAs in serum from CRC patients to demonstrate the underlying molecular networks involved in CRC development and progression, which may serve as disease biomarkers and novel therapeutic targets

RESULTS

DISCUSSION

MATERIALS AND METHODS