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MiR-17-92 cluster is associated with 13q gain and c-myc expression during colorectal adenoma to adenocarcinoma progression.

Diosdado B, van de Wiel MA, Terhaar Sive Droste JS, Mongera S, Postma C, Meijerink WJ, Carvalho B, Meijer GA - Br. J. Cancer (2009)

Bottom Line: From the six members of the miR-17-92 cluster, all except miR-18a, showed significant increased expression in colorectal tumours with miR-17-92 locus gain compared with tumours without miR-17-92 locus gain.Unsupervised cluster analysis clustered the tumours based on the presence of miR-17-92 locus gain.Significant correlation between the expression of c-myc and the six miRNAs was also found.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, VU University medical center Amsterdam, Amsterdam 1081HV, the Netherlands.

ABSTRACT

Background: MicroRNAs are small non-coding RNA molecules, which regulate central mechanisms of tumorigenesis. In colorectal tumours, the combination of gain of 8q and 13q is one of the major factors associated with colorectal adenoma to adenocarcinoma progression. Functional studies on the miR-17-92 cluster localised on 13q31 have shown that its transcription is activated by c-myc, located on 8q, and that it has oncogenic activities. We investigated the contribution of the miR-17-92 cluster during colorectal adenoma to adenocarcinoma progression.

Methods: Expression levels of the miR-17-92 cluster were determined in 55 colorectal tumours and in 10 controls by real-time RT-PCR. Messenger RNA c-myc expression was also determined by real-time RT-PCR in 48 tumours with array comparative genomic hybridisation (aCGH) data available.

Results: From the six members of the miR-17-92 cluster, all except miR-18a, showed significant increased expression in colorectal tumours with miR-17-92 locus gain compared with tumours without miR-17-92 locus gain. Unsupervised cluster analysis clustered the tumours based on the presence of miR-17-92 locus gain. Significant correlation between the expression of c-myc and the six miRNAs was also found.

Conclusion: Increased expression of miR-17-92 cluster during colorectal adenoma to adenocarcinoma progression is associated to DNA copy number gain of miR17-92 locus on 13q31 and c-myc expression.

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Related in: MedlinePlus

Correlation between the expression of the c-myc gene and each of the miRNAs of the miR-17-92 cluster. The scatter plots of c-myc mRNA expression (x axis) and expression of each of the miR-17-92 cluster miRNAs (y axis) show positive correlations.
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fig4: Correlation between the expression of the c-myc gene and each of the miRNAs of the miR-17-92 cluster. The scatter plots of c-myc mRNA expression (x axis) and expression of each of the miR-17-92 cluster miRNAs (y axis) show positive correlations.

Mentions: MiR-17-92 expression has also been shown to be regulated by the transcription factor c-myc, located on 8q24. Consequently, to fully investigate the mechanisms of regulation of the expression of the miR-17-92 cluster during colorectal adenoma to adenocarcinoma progression, we determined the correlation between the c-myc mRNA expression on 48 tumours with miR-17-92 expression data available. c-myc expression levels were significantly correlated to the expression of miR17-5p (r=0.6, P<0.001), miR-18a (r=0.6, P<0.001), miR-20a (r=0.5, P<0.001), miR-19a (r=0.5, P=0.002), miR-19b-1 (r=0.4, P=0.004) and miR-92a-1 (r=0.4, P<0.005) as shown in Figure 4.


MiR-17-92 cluster is associated with 13q gain and c-myc expression during colorectal adenoma to adenocarcinoma progression.

Diosdado B, van de Wiel MA, Terhaar Sive Droste JS, Mongera S, Postma C, Meijerink WJ, Carvalho B, Meijer GA - Br. J. Cancer (2009)

Correlation between the expression of the c-myc gene and each of the miRNAs of the miR-17-92 cluster. The scatter plots of c-myc mRNA expression (x axis) and expression of each of the miR-17-92 cluster miRNAs (y axis) show positive correlations.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2736819&req=5

fig4: Correlation between the expression of the c-myc gene and each of the miRNAs of the miR-17-92 cluster. The scatter plots of c-myc mRNA expression (x axis) and expression of each of the miR-17-92 cluster miRNAs (y axis) show positive correlations.
Mentions: MiR-17-92 expression has also been shown to be regulated by the transcription factor c-myc, located on 8q24. Consequently, to fully investigate the mechanisms of regulation of the expression of the miR-17-92 cluster during colorectal adenoma to adenocarcinoma progression, we determined the correlation between the c-myc mRNA expression on 48 tumours with miR-17-92 expression data available. c-myc expression levels were significantly correlated to the expression of miR17-5p (r=0.6, P<0.001), miR-18a (r=0.6, P<0.001), miR-20a (r=0.5, P<0.001), miR-19a (r=0.5, P=0.002), miR-19b-1 (r=0.4, P=0.004) and miR-92a-1 (r=0.4, P<0.005) as shown in Figure 4.

Bottom Line: From the six members of the miR-17-92 cluster, all except miR-18a, showed significant increased expression in colorectal tumours with miR-17-92 locus gain compared with tumours without miR-17-92 locus gain.Unsupervised cluster analysis clustered the tumours based on the presence of miR-17-92 locus gain.Significant correlation between the expression of c-myc and the six miRNAs was also found.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, VU University medical center Amsterdam, Amsterdam 1081HV, the Netherlands.

ABSTRACT

Background: MicroRNAs are small non-coding RNA molecules, which regulate central mechanisms of tumorigenesis. In colorectal tumours, the combination of gain of 8q and 13q is one of the major factors associated with colorectal adenoma to adenocarcinoma progression. Functional studies on the miR-17-92 cluster localised on 13q31 have shown that its transcription is activated by c-myc, located on 8q, and that it has oncogenic activities. We investigated the contribution of the miR-17-92 cluster during colorectal adenoma to adenocarcinoma progression.

Methods: Expression levels of the miR-17-92 cluster were determined in 55 colorectal tumours and in 10 controls by real-time RT-PCR. Messenger RNA c-myc expression was also determined by real-time RT-PCR in 48 tumours with array comparative genomic hybridisation (aCGH) data available.

Results: From the six members of the miR-17-92 cluster, all except miR-18a, showed significant increased expression in colorectal tumours with miR-17-92 locus gain compared with tumours without miR-17-92 locus gain. Unsupervised cluster analysis clustered the tumours based on the presence of miR-17-92 locus gain. Significant correlation between the expression of c-myc and the six miRNAs was also found.

Conclusion: Increased expression of miR-17-92 cluster during colorectal adenoma to adenocarcinoma progression is associated to DNA copy number gain of miR17-92 locus on 13q31 and c-myc expression.

Show MeSH
Related in: MedlinePlus