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Open Access Highly Accessed Research article

Identifying MicroRNA-mRNA regulatory network in colorectal cancer by a combination of expression profile and bioinformatics analysis

Jihong Fu1, Wentao Tang2, Peng Du1, Guanghui Wang1, Wei Chen1, Jingming Li1, Yunxiang Zhu12, Jun Gao3* and Long Cui1*

Author Affiliations

1 Colorectal Surgery Department, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Kongjiang Road 1665, Shanghai, 200092, China

2 Second Affiliated Hospital, Yangzhou University, Jiangsu, 225001, China

3 Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Changhai Road 168, Shanghai, 200433, China

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BMC Systems Biology 2012, 6:68  doi:10.1186/1752-0509-6-68

Published: 15 June 2012

Abstract

Background

MicroRNAs (miRNAs) are involved in carcinogenesis and tumor progression by regulating post-transcriptional gene expression. However, the miRNA-mRNA regulatory network is far from being fully understood. The objective of this study is to identify the colorectal cancer (CRC) specific miRNAs and their target mRNAs using a multi-step approach.

Results

A multi-step approach combining microarray miRNA and mRNA expression profile and bioinformatics analysis was adopted to identify the CRC specific miRNA-mRNA regulatory network. First, 32 differentially expressed miRNAs and 2916 mRNAs from CRC samples and their corresponding normal epithelial tissues were identified by miRNA and mRNA microarray, respectively. Secondly, 22 dysregulated miRNAs and their 58 target mRNAs (72 miRNA-mRNA pairs) were identified by a combination of Pearson’s correlation analysis and prediction by databases TargetScan and miRanda. Bioinformatics analysis revealed that these miRNA-mRNAs pairs were involved in Wnt signaling pathway. Additionally, 6 up-regulated miRNAs (mir-21, mir-223, mir-224, mir-29a, mir-29b, and mir-27a) and 4 down-regulated predicted target mRNAs (SFRP1, SFRP2, RNF138, and KLF4) were selected to validate the expression level and their anti-correlationship in an extended cohort of CRC patients by qRT-PCR. Except for mir-27a, the differential expression and their anti-correlationship were proven. Finally, a transfection assay was performed to validate a regulatory relationship between mir-29a and KLF4 at both RNA and protein levels.

Conclusions

Seventy-two miRNA-mRNA pairs combined by 22 dysregulated miRNAs and their 58 target mRNAs identified by the multi-step approach appear to be involved in CRC tumorigenesis. The results in our study were worthwhile to further investigation via a functional study to fully understand the underlying regulatory mechanisms of miRNA in CRC.

Keywords:
MicroRNAs; Target mRNAs; Colorectal cancer; Microarray