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Increased microRNA activity in human cancers.

Israel A, Sharan R, Ruppin E, Galun E - PLoS ONE (2009)

Bottom Line: Using the method described here, we quantified miRNA activity in papillary thyroid carcinoma and breast cancer, and found a strong and distinctive signal of increased global miRNA activity, embedded in the pertaining gene expression measurements.Interestingly, we found that in these two cancers, miRNA activity is globally increased, and is associated with a global downregulation of miRNA target genes.This downregulation of miRNA regulated genes is particularly noticeable for genes carrying multiple target sites for miRNAs.

View Article: PubMed Central - PubMed

Affiliation: Goldyne Savad Gene Therapy Institute, Hadassah Hebrew University Hospital, Jerusalem, Israel.

ABSTRACT
MicroRNAs (miRNAs) are small regulatory RNAs that act by blocking the translation and increasing the degradation of target transcripts. MiRNAs play a critical role in many biological processes including development and differentiation and many studies have shown that major changes in miRNA levels occur in cancer. Since miRNAs degrade target messages, we used this property to develop a novel computational method aimed at determining the actual biological activity of miRNAs using variations in gene expression. Using the method described here, we quantified miRNA activity in papillary thyroid carcinoma and breast cancer, and found a strong and distinctive signal of increased global miRNA activity, embedded in the pertaining gene expression measurements. Interestingly, we found that in these two cancers, miRNA activity is globally increased, and is associated with a global downregulation of miRNA target genes. This downregulation of miRNA regulated genes is particularly noticeable for genes carrying multiple target sites for miRNAs. Among the miRNA-repressed genes, we found a significant enrichment of known tumor suppressors, thereby suggesting that the increased miRNA activity was indeed tumorigenic.

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Hierarchical clustering of breast samples by MiR-seed activity scores.Clustering was done by complete linkage on cluster 3.0 according to the correlation (centered) similarity metric, after selecting miR-seeds for which the SD is at least 4. It can be observed that normal samples are clustered together. Most of the BLC tumor samples are also grouped together. Prior to clustering, samples were randomly shuffled. Color code: red means increased activity of miR-seeds; green decreased (Spearman rank correlation, complete linkage).
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pone-0006045-g002: Hierarchical clustering of breast samples by MiR-seed activity scores.Clustering was done by complete linkage on cluster 3.0 according to the correlation (centered) similarity metric, after selecting miR-seeds for which the SD is at least 4. It can be observed that normal samples are clustered together. Most of the BLC tumor samples are also grouped together. Prior to clustering, samples were randomly shuffled. Color code: red means increased activity of miR-seeds; green decreased (Spearman rank correlation, complete linkage).

Mentions: Lu et al. [8] have shown that microRNA levels measured by bead-flow permit the classification of human cancers by non-supervised methods such as hierarchical clustering. To ascertain that the miRNA activity scores computed by MIRABELLE do also provide this level of information, we subjected the miR-seed activity matrix produced for the breast cancer datasetto hierarchical clustering [38]. Interestingly, hierarchical clustering based on activity scores allowed to distinguish between tumor and non-tumor samples (Fig. 2). Moreover, the clustering procedure appears to distinguish between subtypes of tumors, with most BLC samples grouped together.


Increased microRNA activity in human cancers.

Israel A, Sharan R, Ruppin E, Galun E - PLoS ONE (2009)

Hierarchical clustering of breast samples by MiR-seed activity scores.Clustering was done by complete linkage on cluster 3.0 according to the correlation (centered) similarity metric, after selecting miR-seeds for which the SD is at least 4. It can be observed that normal samples are clustered together. Most of the BLC tumor samples are also grouped together. Prior to clustering, samples were randomly shuffled. Color code: red means increased activity of miR-seeds; green decreased (Spearman rank correlation, complete linkage).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2698213&req=5

pone-0006045-g002: Hierarchical clustering of breast samples by MiR-seed activity scores.Clustering was done by complete linkage on cluster 3.0 according to the correlation (centered) similarity metric, after selecting miR-seeds for which the SD is at least 4. It can be observed that normal samples are clustered together. Most of the BLC tumor samples are also grouped together. Prior to clustering, samples were randomly shuffled. Color code: red means increased activity of miR-seeds; green decreased (Spearman rank correlation, complete linkage).
Mentions: Lu et al. [8] have shown that microRNA levels measured by bead-flow permit the classification of human cancers by non-supervised methods such as hierarchical clustering. To ascertain that the miRNA activity scores computed by MIRABELLE do also provide this level of information, we subjected the miR-seed activity matrix produced for the breast cancer datasetto hierarchical clustering [38]. Interestingly, hierarchical clustering based on activity scores allowed to distinguish between tumor and non-tumor samples (Fig. 2). Moreover, the clustering procedure appears to distinguish between subtypes of tumors, with most BLC samples grouped together.

Bottom Line: Using the method described here, we quantified miRNA activity in papillary thyroid carcinoma and breast cancer, and found a strong and distinctive signal of increased global miRNA activity, embedded in the pertaining gene expression measurements.Interestingly, we found that in these two cancers, miRNA activity is globally increased, and is associated with a global downregulation of miRNA target genes.This downregulation of miRNA regulated genes is particularly noticeable for genes carrying multiple target sites for miRNAs.

View Article: PubMed Central - PubMed

Affiliation: Goldyne Savad Gene Therapy Institute, Hadassah Hebrew University Hospital, Jerusalem, Israel.

ABSTRACT
MicroRNAs (miRNAs) are small regulatory RNAs that act by blocking the translation and increasing the degradation of target transcripts. MiRNAs play a critical role in many biological processes including development and differentiation and many studies have shown that major changes in miRNA levels occur in cancer. Since miRNAs degrade target messages, we used this property to develop a novel computational method aimed at determining the actual biological activity of miRNAs using variations in gene expression. Using the method described here, we quantified miRNA activity in papillary thyroid carcinoma and breast cancer, and found a strong and distinctive signal of increased global miRNA activity, embedded in the pertaining gene expression measurements. Interestingly, we found that in these two cancers, miRNA activity is globally increased, and is associated with a global downregulation of miRNA target genes. This downregulation of miRNA regulated genes is particularly noticeable for genes carrying multiple target sites for miRNAs. Among the miRNA-repressed genes, we found a significant enrichment of known tumor suppressors, thereby suggesting that the increased miRNA activity was indeed tumorigenic.

Show MeSH
Related in: MedlinePlus