Abstract
BACKGROUND: Her-2 positive subtype breast cancer is characterized as Her-2 gene amplification with poor survival and increased invasiveness accounting for 20-30% of invasive infiltrated breast cancer. A lncRNA-miRNA-mRNA competing endogenous RNA (ceRNA) network is constructed to detect Her-2 specific RNAs in the development and progression of HER-2 positive breast cancer which may overcoming the anti-HER-2 therapy resistance of breast cancer cells. METHODS: One thousand one hundred and nine breast cancer samples obtained from The Cancer Genome Atlas (TCGA) database were classified into two cohorts including ER+/PR+ (n=461) and ER-/PR- breast cancer (n=152). Differently expressed mRNAs, lncRNAs and miRNAs were screened in ER+/PR+ and ER-/PR- breast cancer cohorts, respectively. lncRNA-miRNA interactions were preformed to predicted and verified by miRcode. miRNA-mRNA interactions were selected to predict targeted mRNAs of miRNAs by miRanda, Targetscan and miRTarBase. RESULTS: lncRNA-miRNA-mRNA ceRNA network was constructed by retained lncRNAs, miRNAs and mRNAs. Fifteen DEmiRNAs, 129 DElncRNAs and 269 DEmRNAs were retained in ER+/PR+ cohort after intersection with DEmiRNAs, DElncRNAs and DEmRNAs between breast cancer and normal tissues. Six hundred and ninety-three DEmRNAs, 25 DEmiRNAs and 364 DElncRNAs were retained in ER-/PR- cohort. ceRNA network in ER+/PR+ breast cancer cohort was constructed of the interactions of 4 DElncRNA-DEmiRNA pairs and 2 DEmiRNA-DEmRNA pairs included 4 DElncRNAs, 1 DEmiRNAs, and 2 DEmRNAs. ceRNA network in ER-/PR- breast cancer cohort was constructed of the interactions of 24 DElncRNA-DEmiRNA pairs and 1 DEmiRNA-DEmRNA pairs included 19 DElncRNAs, 4 DEmiRNAs, and 1 DEmRNA. MIR7-3HG- hsa-mir-204-NTRK2 axis was identified in both ER+/PR+ and ER-/PR- cohort in our study. CONCLUSIONS: Based on the ceRNA hypothesis, a potential Her-2 related regulatory ceRNA networks are constructed which may provide novel insights into the mechanism underlying the biological processes of Her-2 positive breast cancer.