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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

Expression levels of the six miRNA-17-92 cluster members by DNA copy number status of the miR-17-92 locus in 48 colorectal tumours. Box plots with median, 25th and 75th percentiles and range of expression levels of each of the six miRNAs of the miR-17-92 cluster in 48 colorectal tumours showed significantly increased expression in colorectal tumours with miR-17-92 locus gain compared with colorectal tumours without gain of the miR-17-92 locus except miR-18a.
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fig2: Expression levels of the six miRNA-17-92 cluster members by DNA copy number status of the miR-17-92 locus in 48 colorectal tumours. Box plots with median, 25th and 75th percentiles and range of expression levels of each of the six miRNAs of the miR-17-92 cluster in 48 colorectal tumours showed significantly increased expression in colorectal tumours with miR-17-92 locus gain compared with colorectal tumours without gain of the miR-17-92 locus except miR-18a.

Mentions: To study whether DNA copy number gain of miR-17-92 locus in colorectal tumours influences the expression of the miR-17-92 cluster, 48 of the set of 55 colorectal tumours, with aCGH data available were selected. Seventeen tumours (4 adenomas and 13 adenocarcinomas) showed 13q DNA copy number gain and 31 tumours (21 adenomas and 10 adenocarcinomas) did not show gain of the miR-17-92 locus. Comparison of the expression levels of each of the miR-17-92 cluster miRNAs between these two groups showed that expression of miR-17 was increased 1.6-fold (P=0.05) in tumours with miR17-92 locus gain compared with tumours with no miR-17-92 locus gain. In addition, miR-19a showed 1.8 times elevated expression (P<0.01), miR-20a 1.7-fold (P<0.01), miR-19b-1 1.8-fold (P<0.003) and miR-92a-1 2.0 times increased expression (P<0.003). MiR-18a showed a 2.0-fold over expression that did not reach statistical significance (P=0.29) (Figure 2). The multivariate analysis for associating expression values of the entire miR cluster with miR17-92 locus gain revealed a highly significant association (P<0.001).


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)

Expression levels of the six miRNA-17-92 cluster members by DNA copy number status of the miR-17-92 locus in 48 colorectal tumours. Box plots with median, 25th and 75th percentiles and range of expression levels of each of the six miRNAs of the miR-17-92 cluster in 48 colorectal tumours showed significantly increased expression in colorectal tumours with miR-17-92 locus gain compared with colorectal tumours without gain of the miR-17-92 locus except miR-18a.
© Copyright Policy
Related In: Results  -  Collection

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

fig2: Expression levels of the six miRNA-17-92 cluster members by DNA copy number status of the miR-17-92 locus in 48 colorectal tumours. Box plots with median, 25th and 75th percentiles and range of expression levels of each of the six miRNAs of the miR-17-92 cluster in 48 colorectal tumours showed significantly increased expression in colorectal tumours with miR-17-92 locus gain compared with colorectal tumours without gain of the miR-17-92 locus except miR-18a.
Mentions: To study whether DNA copy number gain of miR-17-92 locus in colorectal tumours influences the expression of the miR-17-92 cluster, 48 of the set of 55 colorectal tumours, with aCGH data available were selected. Seventeen tumours (4 adenomas and 13 adenocarcinomas) showed 13q DNA copy number gain and 31 tumours (21 adenomas and 10 adenocarcinomas) did not show gain of the miR-17-92 locus. Comparison of the expression levels of each of the miR-17-92 cluster miRNAs between these two groups showed that expression of miR-17 was increased 1.6-fold (P=0.05) in tumours with miR17-92 locus gain compared with tumours with no miR-17-92 locus gain. In addition, miR-19a showed 1.8 times elevated expression (P<0.01), miR-20a 1.7-fold (P<0.01), miR-19b-1 1.8-fold (P<0.003) and miR-92a-1 2.0 times increased expression (P<0.003). MiR-18a showed a 2.0-fold over expression that did not reach statistical significance (P=0.29) (Figure 2). The multivariate analysis for associating expression values of the entire miR cluster with miR17-92 locus gain revealed a highly significant association (P<0.001).

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