title: Lentiviral vector-mediated shRNA against AIMP2-DX2 suppresses lung cancer cell growth through blocking glucose uptake.
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 capdependent 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.
authors.affiliation: Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul 151-742, Korea.
authors.forename: Seung-Hee
authors.initials: SH
authors.lastname: Chang
authors.forename: Youn-Sun
authors.initials: YS
authors.lastname: Chung
authors.forename: Soon-Kyung
authors.initials: SK
authors.lastname: Hwang
authors.forename: Jung-Taek
authors.initials: JT
authors.lastname: Kwon
authors.forename: Arash
authors.initials: A
authors.lastname: Minai-Tehrani
authors.forename: Sunghoon
authors.initials: S
authors.lastname: Kim
authors.forename: Seung Bum
authors.initials: SB
authors.lastname: Park
authors.forename: Yeon-Soo
authors.initials: YS
authors.lastname: Kim
authors.forename: Myung-Haing
authors.initials: MH
authors.lastname: Cho
mesh_terms: D000604:Amino Acyl-tRNA Synthetases; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D066246:ErbB Receptors / Q000378:metabolism; D005091:Exons; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D005822:Genetic Vectors; D005947:Glucose / Q000378:metabolism*; D051246:Glucose Transport Proteins, Facilitative / Q000235:genetics / Q000378:metabolism; D016695:Glycosyltransferases / Q000378:metabolism; D006056:Golgi Apparatus / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D016086:Lentivirus / Q000235:genetics*; D008175:Lung Neoplasms; D020935:MAP Kinase Signaling System; D009687:Nuclear Proteins; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics*; D059010:Single-Cell Analysis
chemical_list: C575685:AIMP2 protein, human; D002352:Carrier Proteins; D051246:Glucose Transport Proteins, Facilitative; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; C474321:aminoacyl-tRNA synthetase-associated protein p38; D016695:Glycosyltransferases; D066246:ErbB Receptors; D000604:Amino Acyl-tRNA Synthetases; D005947:Glucose