Lentiviral vector-mediated shRNA against AIMP2-DX2 suppresses lung cancer cell growth through blocking glucose uptake

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...

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Bibliographic Details
Published in:Molecules and cells 2012, 33(6), , pp.553-562
Main Authors: Chang, S.H., Seoul National University, Seoul, Republic of Korea, Chung, Y.S., Seoul National University, Seoul, Republic of Korea, Hwang, S.K., National Cancer Institute, Frederick, MD, USA, Kwon, J.T., Seoul National University, Seoul, Republic of Korea, Minai-Tehrani, Arash, Seoul National University, Seoul, Republic of Korea, Kim, S.H., Seoul National University, Seoul, Republic of Korea, Park, S.B., Seoul National University, Seoul, Republic of Korea, Kim, Y.S., Inje University, Seoul, Republic of Korea, Cho, M.H., Seoul National University, Seoul, Republic of Korea
Format: Article
Language:English
Subjects:
AIMP2-DX2
Amino Acyl-tRNA Synthetases
Base Sequence
Biochemistry
Biomedical and Life Sciences
Biomedicine
Biotechnology
Carrier Proteins - genetics
Carrier Proteins - metabolism
Cell Biology
Cell Line, Tumor
Cell Proliferation
CELLS
CELLULE
CELULAS
ErbB Receptors - metabolism
Exons
Gene Expression
Gene Knockdown Techniques
Genetic Vectors
Glucose - metabolism
Glucose Transport Proteins, Facilitative - genetics
Glucose Transport Proteins, Facilitative - metabolism
glucose uptake
gluts
Glycosyltransferases - metabolism
Golgi Apparatus - enzymology
Golgi Apparatus - metabolism
Humans
Lentivirus - genetics
Life Sciences
Lung cancer
Lung Neoplasms
MAP Kinase Signaling System
Nuclear Proteins
Research Article
RNA Interference
RNA, Small Interfering - genetics
Single-Cell Analysis
생물학
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Summary: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.
ISSN:1016-8478
0219-1032
DOI:10.1007/s10059-012-2269-2