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Updated: May 22, 2026
DNA Vector-based RNA Interference to Study Gene Function in Cancer
Published on: June 4, 2012
Lentiviral vector-mediated shRNA against AIMP2-DX2 suppresses lung cancer cell growth through blocking glucose uptake
Seung-Hee Chang1, Youn-Sun Chung, Soon-Kyung Hwang
1Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul 151-742, Korea.
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.
Insights
Aminoacyl-tRNA synthetases [ARS]-interacting multifunctional protein 2 (AIMP2) variant DX2 drives lung cancer progression. Suppressing AIMP2-DX2 with shRNA reduced glucose metabolism, proliferation, and protein translation, suggesting it as a therapeutic target.
Area of Science:
- Molecular Biology
- Cancer Research
- Cell Biology
Background:
- Aminoacyl-tRNA synthetases [ARS]-interacting multifunctional protein 2 (AIMP2) influences cell fate and lung cell differentiation.
- A variant, AIMP2-DX2, is found in cancer cells, with elevated levels noted in NCI-H460 and NCI-H520 lung cell lines.
Purpose of the Study:
- To investigate the functional role of AIMP2-DX2 in lung cancer.
- To evaluate the therapeutic potential of suppressing AIMP2-DX2 using a lentiviral short hairpin RNA (shRNA) system (sh-DX2).
Main Methods:
- Utilized lentivirus-mediated shRNA (sh-DX2) to suppress AIMP2-DX2 expression in NCI-H460 lung cancer cells.
- Assessed changes in glucose uptake, glucose transporters (Gluts), glycosyltransferases (GnT-V and GnT-III), EGFR/MAPK signaling pathway, Ki-67 proliferation marker, and cap-dependent protein translation.
Main Results:
- Suppression of AIMP2-DX2 significantly decreased glucose uptake and Glut expression.
- Down-regulation of AIMP2-DX2 reduced Golgi-associated GnT-V while increasing its antagonist, GnT-III.
- AIMP2-DX2 suppression inhibited the EGFR/MAPK pathway, decreased Ki-67 expression, and reduced cap-dependent protein translation.
Conclusions:
- AIMP2-DX2 plays a crucial role in promoting lung cancer cell proliferation and metabolic activity.
- AIMP2-DX2 represents a potential therapeutic target for lung cancer.
- The sh-DX2 lentiviral system is a viable therapeutic strategy for lung cancer treatment.
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