title: An integrated approach to reveal miRNAs' impacts on the functional consequence of copy number alterations in cancer.
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.
authors.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.
authors.forename: Kening
authors.initials: K
authors.lastname: Li
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China.
authors.forename: Yongjing
authors.initials: Y
authors.lastname: Liu
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China.
authors.forename: Yuanshuai
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Zhao
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China.
authors.forename: Zichuang
authors.initials: Z
authors.lastname: Yan
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China.
authors.forename: Shujuan
authors.initials: S
authors.lastname: Zhang
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China.
authors.forename: Fujun
authors.initials: F
authors.lastname: Qiu
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics; D056915:DNA Copy Number Variations / Q000235:genetics*; D005260:Female; D018628:Gene Dosage; D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009369:Neoplasms / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics
chemical_list: D035683:MicroRNAs