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Journal of Hematology & Oncology
Published in: Journal of Hematology & Oncology 1/2012

Open Access 01-12-2012 | Research

Expression of miR-34 is lost in colon cancer which can be re-expressed by a novel agent CDF

Authors: Sanchita Roy, Edi Levi, Adhip PN Majumdar, Fazlul H Sarkar

Published in: Journal of Hematology & Oncology | Issue 1/2012

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Abstract

Background

Colorectal Cancer (CRC) is one of the leading causes of death worldwide. Numerous cellular events, including deregulated expression of microRNAs (miRNAs), specifically the family of miR-34 consisting of miR-34a, b and c, is known to regulate the processes of growth and metastasis.

Methods

We evaluated the expression of miR-34 in formalin-fixed paraffin-embedded (FFPE) human colon cancer tissue specimens compared to normal colonic mucosa. Moreover, we also assessed the expression of miR-34 in colon cancer cell lines treated with our newly developed synthetic analogue of curcumin referred as difluorinated curcumin (CDF) compared to well known inhibitor of methyl transferase.

Results

We found that the expression of miR-34a and miR-34c was down-regulated in colon cancer specimens compared to normal colonic mucosa and the loss of expression was also consistent with data from colon cancer cell lines. This down-regulation was attributed to promoter hypermethylation, because we found that the treatment of colon cancer cells with 5-aza-2´-deoxycytidine, a methyltransferase inhibitor, markedly induced the levels of miR-34a and miR-34c expression. Likewise, CDF was very effective in the re-expression of miR-34a and miR-34c, which was consistent with inhibition of cell growth of both chemo-sensitive and chemo-resistant colon cancer cells. The re-expression of miR-34 led to a marked reduction in the expression of its target gene, Notch-1.

Conclusion

The loss of expression of miR-34 in colon cancer is in part due to promoter hypermethylation of miR-34, which can be re-expressed with our novel agent CDF, suggesting that CDF could be a novel demethylating agent for restoring the expression of miR-34 family, and thus CDF could become a newer therapeutic agent for the treatment of colon cancer.
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Metadata
Title
Expression of miR-34 is lost in colon cancer which can be re-expressed by a novel agent CDF
Authors
Sanchita Roy
Edi Levi
Adhip PN Majumdar
Fazlul H Sarkar
Publication date
01-12-2012
Publisher
BioMed Central
Published in
Journal of Hematology & Oncology / Issue 1/2012
Electronic ISSN: 1756-8722
DOI
https://doi.org/10.1186/1756-8722-5-58

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