期刊
CANCER LETTERS
卷 309, 期 1, 页码 62-70出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2011.05.017
关键词
miR-17-92 cluster; Myc; Multiple myeloma
类别
资金
- National Natural Science Foundation of China [30971294, 81071946]
- Natural Science Foundation of Jiangsu Province [BK2008465]
- Foundation of Jiangsu Provincial Bureau of Health [H200932]
- Liu Da Ren Cai Gao Feng of Jiangsu Province
- Health Ministry Foundation for Clinical Sciences Development
- National Public Health Grand Research Foundation [201002024]
- Jiangsu Higher Education Institutions
miRNAs play important roles in the regulation of cell proliferation, differentiation and apoptosis. The deregulation of miRNAs expression contributes to tumorigenesis by modulating oncogenic and tumor suppressor signaling pathways. Oncogenic transcription factor Myc can control expression of a large set of microRNAs (miRNAs). Previous studies have shown that the expression of miR-17-92 cluster, a polycistron encoding six microRNAs (miRNA), has close relationship with the expression of Myc. In current study, silencing Myc in multiple myeloma (MM)cells induced cell death and growth inhibition, and down-regulated expression of miR-17-92 cluster. Overexpression of miR-17 or miR-18 could partly abrogated Myc-knockdown-induced MM cell apoptosis. One of the mechanism of Myc inhibiting MM cell apoptosis is through Myc activates miR-17-92 cluster and subsequently down-modulates proapoptotic protein Bim. Although miR-17-92 cluster are located at 13q31.3, the expression of miR-18, miR-19 and miR-20 (especially miR-19) in patients with del(13q14) was higher than those without del(13q14). Patients with miR-17, miR-20 and miR-92 high-expression had shorter PFS compared to those with miR-17, miR-20 and miR-92 low-expression. These results suggest the Myc-inducible miR-17-92 cluster miRNAs contribute to tumorigenesis and poor prognosis in multiple myeloma. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
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