Regulatory network reconstruction of five essential microRNAs for survival analysis in breast cancer by integrating miRNA and mRNA expression datasets.

Regulatory network reconstruction of five essential microRNAs for survival analysis in breast cancer by integrating miRNA and mRNA expression datasets.

Publication date: Mar 12, 2019

Although many of the genetic loci associated with breast cancer risk have been reported, there is a lack of systematic analysis of regulatory networks composed of different miRNAs and mRNAs on survival analysis in breast cancer. To reconstruct the microRNAs-genes regulatory network in breast cancer, we employed the expression data from The Cancer Genome Atlas (TCGA) related to five essential miRNAs including miR-21, miR-22, miR-210, miR-221, and miR-222, and their associated functional genomics data from the GEO database. Then, we performed an integration analysis to identify the essential target factors and interactions for the next survival analysis in breast cancer. Based on the results of our integrated analysis, we have identified significant common regulatory signatures including differentially expressed genes, enriched pathways, and transcriptional regulation such as interferon regulatory factors (IRFs) and signal transducer and activator of transcription 1 (STAT1). Finally, a reconstructed regulatory network of five miRNAs and 34 target factors was established and then applied to survival analysis in breast cancer. When we used expression data for individual miRNAs, only miR-21 and miR-22 were significantly associated with a survival change. However, we identified 45 significant miRNA-gene pairs that predict overall survival in breast cancer out of 170 one-on-one interactions in our reconstructed network covering all of five miRNAs, and several essential factors such as PSMB9, HLA-C, RARRES3, UBE2L6, and NMI. In our study, we reconstructed regulatory network of five essential microRNAs for survival analysis in breast cancer by integrating miRNA and mRNA expression datasets. These results may provide new insights into regulatory network-based precision medicine for breast cancer.

He, K., Li, W.X., Guan, D., Gong, M., Ye, S., Fang, Z., Huang, J.F., and Lu, A. Regulatory network reconstruction of five essential microRNAs for survival analysis in breast cancer by integrating miRNA and mRNA expression datasets. 04205. 2019 Funct Integr Genomics.

Concepts Keywords
Breast Survival breast cancer
Breast Cancer Systematic regulatory networks
Gene Insights regulatory network
Genetic Loci Mir-375
HLA Mir-30 microRNA precursor
MicroRNAs Gene expression
MiRNA Non-coding RNA
MRNA MicroRNA
MRNAs Nucleic acids
Regulatory Networks Genetics
STAT1 Branches of biology
Transcription
Transcriptional Regulation
Transducer

Semantics

Type Source Name
gene UNIPROT NMI
gene UNIPROT MYO1C
gene UNIPROT UBE2L6
gene UNIPROT HLA-C
gene UNIPROT RARRES3
gene UNIPROT PSMB9
gene UNIPROT STAT1
gene UNIPROT MLXIP
gene UNIPROT MYLIP
gene UNIPROT MARCH8
disease DOID Cancer
disease MESH Cancer
pathway BSID Breast cancer
disease DOID breast cancer
disease MESH breast cancer

Original Article

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