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KMID : 0578320120330060553
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Molecules and Cells
2012 Volume.33 No. 6 p.553 ~ p.562
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Lentiviral Vector-Mediated shRNA against AIMP2-DX2 Suppresses Lung Cancer Cell Growth through Blocking Glucose Uptake
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Chang Seung-Hee
Chung Youn-Sun
Hwang Soon-Kyung
Kwon Jung-Taek
Arash Minai-Tehrani
Kim Sung-Hoon
Park Seung-Bum
Kim Yeon-Soo
Cho Myung-Haing
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Abstract
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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.
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KEYWORD
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AIMP2-DX2, EGFR/MAPK signaling pathway, glucose uptake, gluts
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