Construction and Comparison of ceRNA Regulatory Network for Different Age Female Breast Cancer

Abstract

Studies have shown the difference appearing among the prognosis of patients in different age groups. However, the molecular mechanism implicated in this disparity have not been elaborated. In this study, expression profiles of female breast cancer (BRCA) associated mRNAs, lncRNAs and miRNAs were downloaded from the TCGA database. The sample were manually classified into three groups according to their age at initial pathological diagnosis: young (age ≤ 39 years), elderly (age ≥ 65 years), and intermediate (age 40–64 years). lncRNA-miRNA-mRNA competitive endogenous RNA (ceRNA) network was respectively constructed for different age BRCA. Then, the biological functions of differentially expressed mRNAs (DEmRNAs) in ceRNA network were further investigated by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Finally, survival analysis was used to identify prognostic biomarkers for different age BRCA patients. We identified 13 RNAs, 38 RNAs and 40 RNAs specific to patients aged ≤ 39 years, aged 40–64 years, and aged ≥ 65 years, respectively. Furthermore, the unique pathways were mainly enriched in cytokine-cytokine receptor interaction in patients aged 40–64 years, and were mainly enriched in TGF-beta signaling pathway in patients aged ≥ 65 years. According to the survival analysis, AGAP11, has-mir-301b, and OSR1 were respectively functioned as prognostic biomarkers in young, intermediate, and elderly group. In summary, our study identified the differences in the ceRNA regulatory networks and provides an effective bioinformatics basis for further understanding of the pathogenesis and predicting outcomes for different age BRCA.

Identification of a hippocampal lncRNA-regulating network in a natural aging rat model

“…Meanwhile, the lncRNA NEAT1 is involved in neurodegeneration, and suppression of this lncRNA in the hippocampus enhances memory in elderly mice by repressing neuronal histone methylation [ 36 ]. Previous investigations have shown that lncRNAs modulate target gene expression through the ceRNA network and are involved in the development of age-associated disorders [ 37 , 38 ]. lncRNA-ES3 suppresses miR-34c-5p expression through direct interaction, and knockdown of this lncRNA inhibits the senescence of vascular smooth muscle cells, regulated through the lncRNA-ES3/miR-34c-5p/Bcl-2 modifying factor axis [ 39 ].…”

Multivariate competing endogenous RNA network characterization for cancer microRNA biomarker discovery: a novel bioinformatics model with application to prostate cancer metastasis

“…compared ceRNA networks for different ages of women with breast cancer and found prognostic biomarkers specific to each age group. 6 Li et al . extracted survival-related lncRNA–miRNA–mRNA networks for immune infiltration in colorectal cancer by evaluating the expression and prognostic power of dysregulated miRNAs for model training.…”