title: Identification of targets of miRNA-221 and miRNA-222 in fulvestrant-resistant breast cancer.
abstract: The present study aimed to identify the differentially expressed genes (DEGs) regulated by microRNA (miRNA)-221 and miRNA-222 that are associated with the resistance of breast cancer to fulvestrant. The GSE19777 transcription profile was downloaded from the Gene Expression Omnibus database, and includes data from three samples of antisense miRNA-221-transfected fulvestrant-resistant MCF7-FR breast cancer cells, three samples of antisense miRNA-222-transfected fulvestrant-resistant MCF7-FR cells and three samples of control inhibitor (green fluorescent protein)-treated fulvestrant-resistant MCF7-FR cells. The linear models for microarray data package in R/Bioconductor was employed to screen for DEGs in the miRNA-transfected cells, and the pheatmap package in R was used to perform two-way clustering. Pathway enrichment was conducted using the Gene Set Enrichment Analysis tool. Furthermore, a miRNA-messenger (m) RNA regulatory network depicting interactions between miRNA-targeted upregulated DEGs was constructed and visualized using Cytoscape. In total, 492 and 404 DEGs were identified for the antisense miRNA-221-transfected MCF7-FR cells and the antisense miRNA-222-transfected MCF7-FR cells, respectively. Genes of the pentose phosphate pathway (PPP) were significantly enriched in the antisense miRNA-221-transfected MCF7-FR cells. In addition, components of the Wnt signaling pathway and cell adhesion molecules (CAMs) were significantly enriched in the antisense miRNA-222-transfected MCF7-FR cells. In the miRNA-mRNA regulatory network, miRNA-222 was demonstrated to target protocadherin 10 (PCDH10). The results of the present study suggested that the PPP and Wnt signaling pathways, as well as CAMs andPCDH10, may be associated with the resistance of breast cancer to fulvestrant.
authors.affiliation: Department of Lymphoma, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, P.R. China; Tianjin's Clinical Research Center for Cancer, Sino-US Center of Lymphoma and Leukemia, Tianjin 300060, P.R. China.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Liu
authors.affiliation: School of Material Science and Engineering, Heibei University of Technology, Tianjin 300322, P.R. China.
authors.forename: Manna
authors.initials: M
authors.lastname: Sun
authors.affiliation: Department of Radiotherapy, The Second Hospital of Tianjin Medical University, Tianjin 300211, P.R. China.
authors.forename: Wenhua
authors.initials: W
authors.lastname: Jiang
authors.affiliation: Department of Radiology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, P.R. China.
authors.forename: Jinkun
authors.initials: J
authors.lastname: Zhao
authors.affiliation: School of Material Science and Engineering, Heibei University of Technology, Tianjin 300322, P.R. China.
authors.forename: Chunyong
authors.initials: C
authors.lastname: Liang
authors.affiliation: Department of Lymphoma, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, P.R. China; Tianjin's Clinical Research Center for Cancer, Sino-US Center of Lymphoma and Leukemia, Tianjin 300060, P.R. China.
authors.forename: Huilai
authors.initials: H
authors.lastname: Zhang
keywords: breast cancer; fulvestrant resistance; gene set enrichment analysis; microRNA; microarray