RRC ID 43707
著者 Ichikawa T, Sato F, Terasawa K, Tsuchiya S, Toi M, Tsujimoto G, Shimizu K.
タイトル Trastuzumab produces therapeutic actions by upregulating miR-26a and miR-30b in breast cancer cells.
ジャーナル PLoS One
Abstract OBJECTIVE:Trastuzumab has been used for the treatment of HER2-positive breast cancer (BC). However, a subset of BC patients exhibited resistance to trastuzumab therapy. Thus, clarifying the molecular mechanism of trastuzumab treatment will be beneficial to improve the treatment of HER2-positive BC patients. In this study, we identified trastuzumab-responsive microRNAs that are involved in the therapeutic effects of trastuzumab.
METHODS AND RESULTS:RNA samples were obtained from HER2-positive (SKBR3 and BT474) and HER2-negetive (MCF7 and MDA-MB-231) cells with and without trastuzumab treatment for 6 days. Next, we conducted a microRNA profiling analysis using these samples to screen those microRNAs that were up- or down-regulated only in HER2-positive cells. This analysis identified miR-26a and miR-30b as trastuzumab-inducible microRNAs. Transfecting miR-26a and miR-30b induced cell growth suppression in the BC cells by 40% and 32%, respectively. A cell cycle analysis showed that these microRNAs induced G1 arrest in HER2-positive BC cells as trastuzumab did. An Annexin-V assay revealed that miR-26a but not miR-30b induced apoptosis in HER2-positive BC cells. Using the prediction algorithms for microRNA targets, we identified cyclin E2 (CCNE2) as a target gene of miR-30b. A luciferase-based reporter assay demonstrated that miR-30b post-transcriptionally reduced 27% (p = 0.005) of the gene expression by interacting with two binding sites in the 3'-UTR of CCNE2.
CONCLUSION:In BC cells, trastuzumab modulated the expression of a subset of microRNAs, including miR-26a and miR-30b. The upregulation of miR-30b by trastuzumab may play a biological role in trastuzumab-induced cell growth inhibition by targeting CCNE2.
巻・号 7(2)
ページ e31422
公開日 2012-1-1
DOI 10.1371/journal.pone.0031422
PII PONE-D-11-08699
PMID 22384020
PMC PMC3288043
MeSH 3' Untranslated Regions Antibodies, Monoclonal, Humanized / pharmacology* Antineoplastic Agents / pharmacology Breast Neoplasms / metabolism* Cell Cycle Cell Line, Tumor Female Gene Expression Profiling* Gene Expression Regulation, Neoplastic* Genes, Reporter Humans MicroRNAs / biosynthesis* Receptor, ErbB-2 / biosynthesis Trastuzumab
IF 2.74
引用数 80
WOS 分野 ONCOLOGY
リソース情報
ヒト・動物細胞 MDA-MB-453(RCB1192)