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Mol. Cells 2012; 33(6): 553-562

Published online June 30, 2012

https://doi.org/10.1007/s10059-012-2269-2

© The Korean Society for Molecular and Cellular Biology

Lentiviral Vector-Mediated shRNA against AIMP2-DX2 Suppresses Lung Cancer Cell Growth through Blocking Glucose Uptake

Seung-Hee Chang1,9, Youn-Sun Chung1,9, Soon-Kyung Hwang2, Jung-Taek Kwon1,3, Arash Minai-Tehrani1, Sunghoon Kim4, Seung Bum Park5, Yeon-Soo Kim6, and Myung-Haing Cho1,7,8,*

1Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul 151-742, Korea, 2Gene Regulation Section, Laboratory of Cancer Prevention, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA, 3Risk Assessment Division, National Institute of Environmental Research, Incheon 404-708, Korea, 4Medicinal Bioconvergence Research Center, Seoul National University, Seoul 151-742, Korea, 5Department of Chemistry, College of National Science, Seoul National University, Seoul 151-742, Korea, 6Department of Smart Foods and Drugs and Indang Institute of Molecular Biology, Inje University, Seoul 100-032, Korea, 7Department of Nanofusion Technology, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 151-742, Korea, 8Graduate Group of Tumor Biology, Seoul National University, Seoul 151-742, Korea, 9These authors contributed equally to this work.

Correspondence to : *Correspondence: mchotox@snu.ac.kr

Received: November 25, 2011; Revised: March 20, 2012; Accepted: March 22, 2012

Abstract

Aminoacyl-tRNA synthetases [ARS]-interacting multifunctional protein 2 (AIMP2) has been implicated in the control of cell fate and lung cell differentiation. A variant of AIMP2 lacking exon 2 (AIMP2-DX2) is expressed in different cancer cells. We previously studied the expression level of AIMP2-DX2 in several lung cell lines and reported elevated expression levels of AIMP2-DX2 in NCI-H460 and NCI-H520. Here, we report that the suppression of AIMP2-DX2 by lentivirus mediated short hairpin (sh)RNA (sh-DX2) decreased the rate of glucose uptake and glucose transporters (Gluts) in NCI-H460 cells. Down-regulation of AIMP2-DX2 reduced glycosyltransferase (GnT)-V in the Golgi apparatus, while inducing the GnT-V antagonist GnT-III. Down-regulation of AIMP2-DX2 also suppressed the epidermal growth factor receptor/mitogen activated protein kinase (EGFR/MAPK) signaling pathway, leading to the decrease of the proliferation marker Ki-67 expression in nuclei. Furthermore, dual luciferase activity reduced cap-dependent protein translation in cells infected with sh-DX2. These results suggest that AIMP2-DX2 may be a relevant therapeutic target for lung cancer, and that the sh-DX2 lentiviral system can be an appropriate method for lung cancer therapy.

Keywords AIMP2-DX2, EGFR/MAPK signaling pathway, glucose uptake, gluts

Article

Research Article

Mol. Cells 2012; 33(6): 553-562

Published online June 30, 2012 https://doi.org/10.1007/s10059-012-2269-2

Copyright © The Korean Society for Molecular and Cellular Biology.

Lentiviral Vector-Mediated shRNA against AIMP2-DX2 Suppresses Lung Cancer Cell Growth through Blocking Glucose Uptake

Seung-Hee Chang1,9, Youn-Sun Chung1,9, Soon-Kyung Hwang2, Jung-Taek Kwon1,3, Arash Minai-Tehrani1, Sunghoon Kim4, Seung Bum Park5, Yeon-Soo Kim6, and Myung-Haing Cho1,7,8,*

1Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul 151-742, Korea, 2Gene Regulation Section, Laboratory of Cancer Prevention, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA, 3Risk Assessment Division, National Institute of Environmental Research, Incheon 404-708, Korea, 4Medicinal Bioconvergence Research Center, Seoul National University, Seoul 151-742, Korea, 5Department of Chemistry, College of National Science, Seoul National University, Seoul 151-742, Korea, 6Department of Smart Foods and Drugs and Indang Institute of Molecular Biology, Inje University, Seoul 100-032, Korea, 7Department of Nanofusion Technology, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 151-742, Korea, 8Graduate Group of Tumor Biology, Seoul National University, Seoul 151-742, Korea, 9These authors contributed equally to this work.

Correspondence to:*Correspondence: mchotox@snu.ac.kr

Received: November 25, 2011; Revised: March 20, 2012; Accepted: March 22, 2012

Abstract

Aminoacyl-tRNA synthetases [ARS]-interacting multifunctional protein 2 (AIMP2) has been implicated in the control of cell fate and lung cell differentiation. A variant of AIMP2 lacking exon 2 (AIMP2-DX2) is expressed in different cancer cells. We previously studied the expression level of AIMP2-DX2 in several lung cell lines and reported elevated expression levels of AIMP2-DX2 in NCI-H460 and NCI-H520. Here, we report that the suppression of AIMP2-DX2 by lentivirus mediated short hairpin (sh)RNA (sh-DX2) decreased the rate of glucose uptake and glucose transporters (Gluts) in NCI-H460 cells. Down-regulation of AIMP2-DX2 reduced glycosyltransferase (GnT)-V in the Golgi apparatus, while inducing the GnT-V antagonist GnT-III. Down-regulation of AIMP2-DX2 also suppressed the epidermal growth factor receptor/mitogen activated protein kinase (EGFR/MAPK) signaling pathway, leading to the decrease of the proliferation marker Ki-67 expression in nuclei. Furthermore, dual luciferase activity reduced cap-dependent protein translation in cells infected with sh-DX2. These results suggest that AIMP2-DX2 may be a relevant therapeutic target for lung cancer, and that the sh-DX2 lentiviral system can be an appropriate method for lung cancer therapy.

Keywords: AIMP2-DX2, EGFR/MAPK signaling pathway, glucose uptake, gluts

Mol. Cells
Sep 30, 2022 Vol.45 No.9, pp. 603~672
COVER PICTURE
The Target of Rapamycin Complex (TORC) is a central regulatory hub in eukaryotes, which is well conserved in diverse plant species, including tomato (Solanum lycopersicum). Inhibition of TORC genes (SlTOR, SlLST8, and SlRAPTOR) by VIGS (virus-induced gene silencing) results in early fruit ripening in tomato. The red/ orange tomatoes are early-ripened TORC-silenced fruits, while the green tomato is a control fruit. Top, left, control fruit (TRV2-myc); top, right, TRV2-SlLST8; bottom, left, TRV2-SlTOR; bottom, right, TRV2-SlRAPTOR(Choi et al., pp. 660-672).

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