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

Seung Hee Chang, Youn Sun Chung, Soon Kyung Hwang, Jung Taek Kwon, Arash Minai-Tehrani, Sunghoon Kim, Seung Bum Park, Yeon Soo Kim, Myung Haing Cho

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)553-562
Number of pages10
JournalMolecules and cells
Volume33
Issue number6
DOIs
Publication statusPublished - 2012 Jun

Bibliographical note

Funding Information:
This work was supported by the National Research Found ation grants (NRF-2012-0001116) from the Ministry of Education, Science and Technology (MEST) and M.H. Cho was also partially supported by the Research Institute for Veterinary Science, Seoul National University.

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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