MicroRNA-143 targets DNA methyltransferases 3A in colorectal cancer
| Autor: | Hc C. Jin, Wp P. Tsang, Christoph Röcken, Tt T. Kwok, S S M Ng, Eko K. O. Ng, Jjy Sung, Jun Yu, Jj J. Li, Mpa P. A. Ebert |
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| Rok vydání: | 2009 |
| Předmět: |
Colorectal Neoplasms - enzymology - genetics
Cancer Research Pathology medicine.medical_specialty Methyltransferase Tumor suppressor gene Colorectal cancer Blotting Western MiR-143 Down-Regulation Biology DNA Methyltransferase 3A RNA interference Cell Line Tumor microRNA medicine Humans Gene silencing DNA (Cytosine-5-)-Methyltransferases Gene Silencing RNA Small Interfering Molecular Diagnostics MicroRNAs - genetics - metabolism Regulation of gene expression Reverse Transcriptase Polymerase Chain Reaction Cancer medicine.disease Gene Expression Regulation Neoplastic MicroRNAs Oncology DNA (Cytosine-5-)-Methyltransferase - metabolism Cancer research DNMT3A Gene Expression Regulation Neoplastic - genetics Colorectal Neoplasms Tumour suppressor |
| Zdroj: | British Journal of Cancer |
| ISSN: | 1532-1827 0007-0920 |
| DOI: | 10.1038/sj.bjc.6605195 |
| Popis: | Background:MicroRNAs (miRNAs) are 19-25-nucleotides regulatory non-protein-coding RNA molecules that regulate the expressions of a wide variety of genes, including some involved in cancer development. In this study, we investigated the possible role of miR-143 in colorectal cancer (CRC).Methods:Expression levels of human mature miRNAs were examined using real-time PCR-based expression arrays on paired colorectal carcinomas and adjacent non-cancerous colonic tissues. The downregulation of miR-143 was further evaluated in colon cancer cell lines and in paired CRC and adjacent non-cancerous colonic tissues by qRT-PCR. Potential targets of miR-143 were defined. The functional effect of miR-143 and its targets was investigated in human colon cancer cell lines to confirm miRNA-target association.Results:Both real-time PCR-based expression arrays and qRT-PCR showed that miR-143 was frequently downregulated in 87.5% (35 of 40) of colorectal carcinoma tissues compared with their adjacent non-cancerous colonic tissues. Using in silico predictions, DNA methyltranferase 3A (DNMT3A) was defined as a potential target of miR-143. Restoration of the miR-143 expression in colon cell lines decreased tumour cell growth and soft-agar colony formation, and downregulated the DNMT3A expression in both mRNA and protein levels. DNMT3A was shown to be a direct target of miR-143 by luciferase reporter assay. Furthermore, the miR-143 expression was observed to be inversely correlated with DNMT3A mRNA and protein expression in CRC tissues.Conclusion:Our findings suggest that miR-143 regulates DNMT3A in CRC. These findings elucidated a tumour-suppressive role of miR-143 in the epigenetic aberration of CRC, providing a potential development of miRNA-based targeted approaches for CRC therapy. © 2009 Cancer Research UK. published_or_final_version |
| Databáze: | OpenAIRE |
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