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

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. METHOD...

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Autores principales: Roy, Sanchita, Levi, Edi, Majumdar, Adhip PN, Sarkar, Fazlul H
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3464169/
https://www.ncbi.nlm.nih.gov/pubmed/22992310
http://dx.doi.org/10.1186/1756-8722-5-58
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author Roy, Sanchita
Levi, Edi
Majumdar, Adhip PN
Sarkar, Fazlul H
author_facet Roy, Sanchita
Levi, Edi
Majumdar, Adhip PN
Sarkar, Fazlul H
author_sort Roy, Sanchita
collection PubMed
description 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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spelling pubmed-34641692012-10-05 Expression of miR-34 is lost in colon cancer which can be re-expressed by a novel agent CDF Roy, Sanchita Levi, Edi Majumdar, Adhip PN Sarkar, Fazlul H J Hematol Oncol Research 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. BioMed Central 2012-09-19 /pmc/articles/PMC3464169/ /pubmed/22992310 http://dx.doi.org/10.1186/1756-8722-5-58 Text en Copyright ©2012 Roy; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Roy, Sanchita
Levi, Edi
Majumdar, Adhip PN
Sarkar, Fazlul H
Expression of miR-34 is lost in colon cancer which can be re-expressed by a novel agent CDF
title Expression of miR-34 is lost in colon cancer which can be re-expressed by a novel agent CDF
title_full Expression of miR-34 is lost in colon cancer which can be re-expressed by a novel agent CDF
title_fullStr Expression of miR-34 is lost in colon cancer which can be re-expressed by a novel agent CDF
title_full_unstemmed Expression of miR-34 is lost in colon cancer which can be re-expressed by a novel agent CDF
title_short Expression of miR-34 is lost in colon cancer which can be re-expressed by a novel agent CDF
title_sort expression of mir-34 is lost in colon cancer which can be re-expressed by a novel agent cdf
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3464169/
https://www.ncbi.nlm.nih.gov/pubmed/22992310
http://dx.doi.org/10.1186/1756-8722-5-58
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