title: MicroRNA expression profiling and bioinformatics analysis of dysregulated microRNAs in vinorelbine-resistant breast cancer cells.
abstract: Vinorelbine (NVB) is one of the most active cytotoxic agents in breast cancer, especially metastatic breast cancer. However, breast cancer patients who are treated with the drug often develop resistance to it and some other drugs. Recently studies have shown that microRNAs (miRNAs) play an important role in drug resistance. In present study, miRNA expression profiles of breast cancer cells MDA-MB-231/S and its NVB-resistant variant MDA-MB-231/NVB cells were analyzed using microarray and the results were confirmed by real-time quantitative polymerase chain reaction. Bioinformatic analyses were carried out to predict gene targets of the dysregulated miRNAs and to analyze their potential roles in the development of drug resistance. Here, 123 differentially expressed miRNAs were identified in the resistant subline compared to MDA-MB-231/S. Networks of KEGG pathways, Gene Ontology (GO) terms, and protein-protein interaction (PPI) of 17 specific selected dysregulated miRNAs were constructed. The results showed that MAPK, mTOR, Wnt, and TGF-beta signaling pathways and several target genes such as CCND1, GRB2 and NT5E may associate with drug resistance of breast cancer cells to NVB. In summary, this study demonstrates that altered miRNA expression pattern is involved in acquiring resistance to NVB in breast cancer MDA-MB-231 cells. All these analysis results provided us a comprehensive view of the function of differential expression miRNAs related to drug resistance of breast cancer and may be helpful for the further study.
authors.affiliation: Center of Clinical Laboratory Science, Jiangsu Cancer Hospital Affiliated to Nanjing Medical University, Nanjing 210009, China.
authors.forename: Shanliang
authors.initials: S
authors.lastname: Zhong
authors.affiliation: Center of Clinical Laboratory Science, Jiangsu Cancer Hospital Affiliated to Nanjing Medical University, Nanjing 210009, China.
authors.forename: Tengfei
authors.initials: T
authors.lastname: Ma
authors.affiliation: Center of Clinical Laboratory Science, Jiangsu Cancer Hospital Affiliated to Nanjing Medical University, Nanjing 210009, China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Zhang
authors.affiliation: The Fourth Clinical School of Nanjing Medical University, Nanjing 210029, China.
authors.forename: Mengmeng
authors.initials: M
authors.lastname: Lv
authors.affiliation: Department of Oncology, Xuzhou Medical College, Xuzhou 221004, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of General Surgery, Jiangsu Cancer Hospital Affiliated to Nanjing Medical University, Nanjing 210009, China.
authors.forename: Jinhai
authors.initials: J
authors.lastname: Tang
authors.affiliation: Center of Clinical Laboratory Science, Jiangsu Cancer Hospital Affiliated to Nanjing Medical University, Nanjing 210009, China. Electronic address: jhzhao2838@sina.com.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Zhao
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053858:Metabolic Networks and Pathways; D035683:MicroRNAs / Q000235:genetics*; D014747:Vinblastine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000077235:Vinorelbine
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D035683:MicroRNAs; D014747:Vinblastine; D000077235:Vinorelbine
keywords: Breast cancer; Chemotherapy; Resistance; miRNAs