Systematic analysis of microRNA involved in resistance of the MCF-7 human breast cancer cell to doxorubicin.
Multidrug resistance remains a major clinical obstacle to successful treatment of breast cancer and leads to poor prognosis for the patients. Recently studies have shown that microRNAs play an important role in breast cancer cell resistance to chemotherapeutic agents. In this study, microRNA expression profiles of MCF-7/AdrVp and MCF-7 were analyzed using microarray and the results were confirmed by real-time RT-polymerase chain reaction. Gene Ontology (GO) and pathways mapping tools were employed to analyse systemically the biological processes and signaling pathways affected by differential expression microRNAs. Here, we showed that 181 human microRNAs were differentially expressed between two cell lines. Compared to MCF-7 cells, there were 16 microRNAs down-regulated and 165 microRNAs up-regulated in MCF-7/AdrVp. Western blot confirmed the correlation between specific microRNA expression and corresponding changes in protein levels of their targets, specifically those that have a documented role in cancer drug resistance. Furthermore, we validated that signaling pathway highlighted in the study was involved in drug resistance. These results indicated that breast cancer cell resistant to chemotherapy was associated with a group of microRNAs. GO and pathway mapping are valid and effective approach to analyse the function of microRNAs and the results could be a guideline for further investigation.
Chen
Guo-Qing
GQ
Department of Human Anatomy, West China School of Preclinical and Forensic Medicine, Sichuan University, Renmin South Road No 17, Chengdu, China.
Zhao
Zhi-Wei
ZW
Zhou
Hong-Ying
HY
Liu
Yuan-Jie
YJ
Yang
Hui-Jun
HJ
D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000494:pharmacology / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects* / Q000235:genetics*; D005260:Female; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D035683:MicroRNAs; D004317:Doxorubicin