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BMC Cancer
Published in: BMC Cancer 1/2009

Open Access 01-12-2009 | Research article

Human colon cancer profiles show differential microRNA expression depending on mismatch repair status and are characteristic of undifferentiated proliferative states

Authors: Aaron L Sarver, Amy J French, Pedro M Borralho, Venugopal Thayanithy, Ann L Oberg, Kevin AT Silverstein, Bruce W Morlan, Shaun M Riska, Lisa A Boardman, Julie M Cunningham, Subbaya Subramanian, Liang Wang, Tom C Smyrk, Cecilia MP Rodrigues, Stephen N Thibodeau, Clifford J Steer

Published in: BMC Cancer | Issue 1/2009

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Abstract

Background

Colon cancer arises from the accumulation of multiple genetic and epigenetic alterations to normal colonic tissue. microRNAs (miRNAs) are small, non-coding regulatory RNAs that post-transcriptionally regulate gene expression. Differential miRNA expression in cancer versus normal tissue is a common event and may be pivotal for tumor onset and progression.

Methods

To identify miRNAs that are differentially expressed in tumors and tumor subtypes, we carried out highly sensitive expression profiling of 735 miRNAs on samples obtained from a statistically powerful set of tumors (n = 80) and normal colon tissue (n = 28) and validated a subset of this data by qRT-PCR.

Results

Tumor specimens showed highly significant and large fold change differential expression of the levels of 39 miRNAs including miR-135b, miR-96, miR-182, miR-183, miR-1, and miR-133a, relative to normal colon tissue. Significant differences were also seen in 6 miRNAs including miR-31 and miR-592, in the direct comparison of tumors that were deficient or proficient for mismatch repair. Examination of the genomic regions containing differentially expressed miRNAs revealed that they were also differentially methylated in colon cancer at a far greater rate than would be expected by chance. A network of interactions between these miRNAs and genes associated with colon cancer provided evidence for the role of these miRNAs as oncogenes by attenuation of tumor suppressor genes.

Conclusion

Colon tumors show differential expression of miRNAs depending on mismatch repair status. miRNA expression in colon tumors has an epigenetic component and altered expression that may reflect a reversion to regulatory programs characteristic of undifferentiated proliferative developmental states.
Appendix
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Metadata
Title
Human colon cancer profiles show differential microRNA expression depending on mismatch repair status and are characteristic of undifferentiated proliferative states
Authors
Aaron L Sarver
Amy J French
Pedro M Borralho
Venugopal Thayanithy
Ann L Oberg
Kevin AT Silverstein
Bruce W Morlan
Shaun M Riska
Lisa A Boardman
Julie M Cunningham
Subbaya Subramanian
Liang Wang
Tom C Smyrk
Cecilia MP Rodrigues
Stephen N Thibodeau
Clifford J Steer
Publication date
01-12-2009
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2009
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-9-401

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