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.
Skip Nav Destination
Article navigation
September 2013
-
Cover Image
Cover Image
- PDF Icon PDF LinkFront Matter
- PDF Icon PDF LinkTable of Contents
- PDF Icon PDF LinkEditorial Board
Research Article|
August 29 2013
Chemical suppression of an oncogenic splicing variant of AIMP2 induces tumour regression
Hee Sook Lee;
Hee Sook Lee
1
*Medicinal Bioconvergence Research Center and College of Pharmacy, Seoul National University, Seoul 305-343, Korea
Search for other works by this author on:
Dae Gyu Kim;
Dae Gyu Kim
1
*Medicinal Bioconvergence Research Center and College of Pharmacy, Seoul National University, Seoul 305-343, Korea
Search for other works by this author on:
Young Sun Oh;
Young Sun Oh
1
*Medicinal Bioconvergence Research Center and College of Pharmacy, Seoul National University, Seoul 305-343, Korea
†Department of Biological Science and the Basic Science Research Institute, Sungkyunkwan University, Suwon 151-742, Korea
Search for other works by this author on:
Nam Hoon Kwon;
Nam Hoon Kwon
*Medicinal Bioconvergence Research Center and College of Pharmacy, Seoul National University, Seoul 305-343, Korea
Search for other works by this author on:
Jin Young Lee;
Jin Young Lee
*Medicinal Bioconvergence Research Center and College of Pharmacy, Seoul National University, Seoul 305-343, Korea
Search for other works by this author on:
Doyeun Kim;
Doyeun Kim
*Medicinal Bioconvergence Research Center and College of Pharmacy, Seoul National University, Seoul 305-343, Korea
Search for other works by this author on:
Song-Hwa Park;
Song-Hwa Park
*Medicinal Bioconvergence Research Center and College of Pharmacy, Seoul National University, Seoul 305-343, Korea
Search for other works by this author on:
Jong-Hwan Song;
Jong-Hwan Song
‡Bio-Organic Science Division, Korea Research Institute of Chemical Technology, Daejeon 440-746, Korea
Search for other works by this author on:
Sunkyung Lee;
Sunkyung Lee
‡Bio-Organic Science Division, Korea Research Institute of Chemical Technology, Daejeon 440-746, Korea
Search for other works by this author on:
Jung Min Han;
Jung Min Han
*Medicinal Bioconvergence Research Center and College of Pharmacy, Seoul National University, Seoul 305-343, Korea
Search for other works by this author on:
Bum-Joon Park;
Bum-Joon Park
§Department of Molecular Biology, College of Natural Science, Pusan National University, Busan 609-735, Korea
Search for other works by this author on:
Jongkook Lee;
Jongkook Lee
∥College of Pharmacy, Kangwon National University, Chuncheon, Gangwon 200-701, Korea
Search for other works by this author on:
Sunghoon Kim
Sunghoon Kim
2
*Medicinal Bioconvergence Research Center and College of Pharmacy, Seoul National University, Seoul 305-343, Korea
¶Department of Molecular Medicine and Biopharmaceutical Sciences and Graduate School for Convergence Technologies, Seoul National University, Seoul 151-742, Korea
2To whom correspondence should be addressed (email sungkim@snu.ac.kr).
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
April 19 2013
Revision Received:
June 28 2013
Accepted:
July 01 2013
Accepted Manuscript online:
July 01 2013
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2013 Biochemical Society
2013
Biochem J (2013) 454 (3): 411–416.
Article history
Received:
April 19 2013
Revision Received:
June 28 2013
Accepted:
July 01 2013
Accepted Manuscript online:
July 01 2013
Citation
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; Chemical suppression of an oncogenic splicing variant of AIMP2 induces tumour regression. Biochem J 15 September 2013; 454 (3): 411–416. doi: https://doi.org/10.1042/BJ20130550
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Captcha Validation Error. Please try again.