Chemical suppression of an oncogenic splicing variant of AIMP2 induces tumour regression

Hee Sook Lee, Dae Gyu Kim, Young Sun Oh, Nam Hoon Kwon, Jin Young Lee, Doyeun Kim, Song Hwa Park, Jong Hwan Song, Sunkyung Lee, Jung Min Han, Bum Joon Park, Jongkook Lee, Sunghoon Kim

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10 Citations (Scopus)

Abstract

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-DXI01, 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-DXI01 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.

Original languageEnglish
Pages (from-to)411-416
Number of pages6
JournalBiochemical Journal
Volume454
Issue number3
DOIs
Publication statusPublished - 2013 Sep 15

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Lee, H. S., Kim, D. G., Oh, Y. S., Kwon, N. H., Lee, J. Y., Kim, D., Park, S. H., Song, J. H., Lee, S., Han, J. M., Park, B. J., Lee, J., & Kim, S. (2013). Chemical suppression of an oncogenic splicing variant of AIMP2 induces tumour regression. Biochemical Journal, 454(3), 411-416. https://doi.org/10.1042/BJ20130550