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An integrated approach to reveal miRNAs' impacts on the functional consequence of copy number alterations in cancer.

Li K, Liu Y, Zhou Y, Zhang R, Zhao N, Yan Z, Zhang Q, Zhang S, Qiu F, Xu Y - Sci Rep (2015)

Bottom Line: Currently, no high-throughput method has been available for identifying the regulatory factors affecting the functional consequences of CNA, and determining their effects on cancer.The results show that miRNAs can modulate oncogenic biological functions by regulating the genes within the CNA regions, and thus play a role as a trigger or balancer in cancer, affecting cancer processes, even survival.Besides, new cancer-related miRNAs were identified.

View Article: PubMed Central - PubMed

Affiliation: 1] College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China [2] School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China.

ABSTRACT
Copy number alteration (CNA) is known to induce gene expression changes mainly through dosage effect, and therefore affect the initiation and progression of tumor. However, tumor samples exhibit heterogeneity in gene dosage sensitivity due to the complicated mechanisms of transcriptional regulation. Currently, no high-throughput method has been available for identifying the regulatory factors affecting the functional consequences of CNA, and determining their effects on cancer. In view of the important regulatory role of miRNA, we investigated the influence of miRNAs on the dosage sensitivities of genes within the CNA regions. By integrating copy number, mRNA expression, miRNA expression profiles of three kinds of cancer, we observed a tendency for high dosage-sensitivity genes to be more targeted by miRNAs in cancer, and identified the miRNAs regulating the dosage sensitivity of amplified/deleted target genes. The results show that miRNAs can modulate oncogenic biological functions by regulating the genes within the CNA regions, and thus play a role as a trigger or balancer in cancer, affecting cancer processes, even survival. This work provided a framework for analyzing the regulation of dosage effect, which will shed a light on understanding the oncogenic and tumor suppressive mechanisms of CNA. Besides, new cancer-related miRNAs were identified.

No MeSH data available.


Related in: MedlinePlus

Dosage sensitivity regulation network in breast cancer.Blue rounded rectangle nodes denote for miRNA, yellow nodes denote for amplified genes, purple nodes denote for deleted genes, pink nodes denote for the genes which are amplified in some samples, and deleted in the other samples.
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f5: Dosage sensitivity regulation network in breast cancer.Blue rounded rectangle nodes denote for miRNA, yellow nodes denote for amplified genes, purple nodes denote for deleted genes, pink nodes denote for the genes which are amplified in some samples, and deleted in the other samples.

Mentions: All these relationships between miRNA and gene dosage sensitivity could form a dosage sensitivity regulatory network (Fig. 5). The dosage sensitivity regulatory network of BRCA contains 140 miRNAs, 196 amplified genes, 78 deleted genes, and 30 ‘flexible’ genes that are amplified in some samples and deleted in the other samples. The GBM network contains 226 miRNAs, 179 amplified genes, 102 deleted genes, and 74 ‘flexible’ genes (Supplementary Fig. S4). The OV network contains 338 miRNAs, 283 amplified genes, 244 deleted genes, and 114 ‘flexible’ genes (Supplementary Fig. S5).


An integrated approach to reveal miRNAs' impacts on the functional consequence of copy number alterations in cancer.

Li K, Liu Y, Zhou Y, Zhang R, Zhao N, Yan Z, Zhang Q, Zhang S, Qiu F, Xu Y - Sci Rep (2015)

Dosage sensitivity regulation network in breast cancer.Blue rounded rectangle nodes denote for miRNA, yellow nodes denote for amplified genes, purple nodes denote for deleted genes, pink nodes denote for the genes which are amplified in some samples, and deleted in the other samples.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4477324&req=5

f5: Dosage sensitivity regulation network in breast cancer.Blue rounded rectangle nodes denote for miRNA, yellow nodes denote for amplified genes, purple nodes denote for deleted genes, pink nodes denote for the genes which are amplified in some samples, and deleted in the other samples.
Mentions: All these relationships between miRNA and gene dosage sensitivity could form a dosage sensitivity regulatory network (Fig. 5). The dosage sensitivity regulatory network of BRCA contains 140 miRNAs, 196 amplified genes, 78 deleted genes, and 30 ‘flexible’ genes that are amplified in some samples and deleted in the other samples. The GBM network contains 226 miRNAs, 179 amplified genes, 102 deleted genes, and 74 ‘flexible’ genes (Supplementary Fig. S4). The OV network contains 338 miRNAs, 283 amplified genes, 244 deleted genes, and 114 ‘flexible’ genes (Supplementary Fig. S5).

Bottom Line: Currently, no high-throughput method has been available for identifying the regulatory factors affecting the functional consequences of CNA, and determining their effects on cancer.The results show that miRNAs can modulate oncogenic biological functions by regulating the genes within the CNA regions, and thus play a role as a trigger or balancer in cancer, affecting cancer processes, even survival.Besides, new cancer-related miRNAs were identified.

View Article: PubMed Central - PubMed

Affiliation: 1] College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China [2] School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China.

ABSTRACT
Copy number alteration (CNA) is known to induce gene expression changes mainly through dosage effect, and therefore affect the initiation and progression of tumor. However, tumor samples exhibit heterogeneity in gene dosage sensitivity due to the complicated mechanisms of transcriptional regulation. Currently, no high-throughput method has been available for identifying the regulatory factors affecting the functional consequences of CNA, and determining their effects on cancer. In view of the important regulatory role of miRNA, we investigated the influence of miRNAs on the dosage sensitivities of genes within the CNA regions. By integrating copy number, mRNA expression, miRNA expression profiles of three kinds of cancer, we observed a tendency for high dosage-sensitivity genes to be more targeted by miRNAs in cancer, and identified the miRNAs regulating the dosage sensitivity of amplified/deleted target genes. The results show that miRNAs can modulate oncogenic biological functions by regulating the genes within the CNA regions, and thus play a role as a trigger or balancer in cancer, affecting cancer processes, even survival. This work provided a framework for analyzing the regulation of dosage effect, which will shed a light on understanding the oncogenic and tumor suppressive mechanisms of CNA. Besides, new cancer-related miRNAs were identified.

No MeSH data available.


Related in: MedlinePlus