Construction of differentially expressed Her-2 related lncrna-mrna-mirna cerna network in Her-2 positive breast cancer

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.