期刊
BIOCHEMICAL JOURNAL
卷 454, 期 -, 页码 411-416出版社
PORTLAND PRESS LTD
DOI: 10.1042/BJ20130550
关键词
aminoacyl-tRNA synthetase-interacting multifunctional protein 2 (AIMP2)-DX2; chemical suppression; lung cancer; mRNA; splicing variant
资金
- National Research Foundation [NRF-2011-0032185, NRF-2011-0031420, NRF-M1AXA002-2010-0029785]
- Ministry of Education, Science and Technology of Korea
- Gyeonggi Research Development Program
AIMP2 (aminoacyl-tRNA synthetase-interacting multifunctional protein 2) is a potent tumour suppressor that induces apoptosis in response to various oncogenic signals. AIMP2-DX2, an exon2-deleted splicing variant of AIMP2, is up-regulated in lung cancer and competitively suppresses the pro-apoptotic activity of AIMP2, resulting in tumorigenesis. In the present study we report that BC-DX101, a synthetic compound, specifically reduces the cellular levels of AIMP2-DX2 through selective degradation of the AIMP2-DX2 mRNA transcript. We found that BC-DXI01-mediated cell death positively correlates with AIMP2-DX2 expression in the lung cancer cell lines tested. Administration of BC-DX101 in a AIMP2-DX2-driven tumour xenograft mice model led to reduced tumour sizes and volumes of up to 60 % in comparison with vehicle-treated mice group, consistent with decreases in AIMP2-DX2 transcript and protein levels. Taken together, our findings suggest that tumorigenic activity of AIMP2-DX2 can be controlled by the small chemical BC-DXI01, which can selectively suppress the AIMP2-DX2 mRNA transcript.
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