Page 101 - D. Cancer biology

Leucyl-tRNA synthetase regulates cell proliferation and invasion in
human colorectal cancer cells

Sang-Heum Han , Su Jeong Park , Jun Gi Cho , Joo-In Park 1,2
1
1
1,2
1 Department of Biochemistry, Dong-A University College of Medicine, Busan, South Korea; Peripheral
2
Neuropathy Research Center, Dong-A University, Busan, South Korea
Abstract Introduction
Leucyl-tRNA synthetase (LARS) senses intracellular leucine and activates Aminoacyl-tRNA synthetases (aaRSs) catalyze the attachment of
mechanistic target of rapamycin complex 1 (mTORC1). Several studies amino acids to their respective tRNAs and play an important role in
suggest that LARS can be a potential target of anticancer agents. However, the maintenance of cell survival. Among them, Leucyl-tRNA
the detailed molecular mechanisms of LARS on the cell proliferation and synthetase (LARS) catalyzes the covalent ligation of leucine to
invasion in human colorectal cancer cells are clearly undefined. In this study, tRNA Leu during polypeptide synthesis. It also acts as a leucine
to clarify the molecular mechanisms of LARS actions in tumor progression, sensor in the mechanistic target of rapamycin complex 1 (mTORC1)
we established LARS-overexpressing stable SW480 cells and LARS-knocked pathway. It was reported that LARS expression was elevated in lung
down stable SW620 cells, and then performed cell proliferation, migration cancer cell line and primary lung cancer tissues. LARS gene is
and transwell invasion assay. LARS overexpression enhances cell amplified in 17% of renal cell carcinoma and mutated/amplified in 4%
proliferation, migration, and invasion, and LARS knockdown reduces them. of malignant peripheral nerve sheet tumor, small cell lung carcinoma,
We examined the expression of several molecules related with cell and melanoma. A previous study demonstrated that knockdown of
proliferation and invasion by western blot analysis. Expression of cyclin D1, LARS inhibits cell migration and colony forming ability in lung
c-Myc, and vimentin was decreased by LARS knockdown. These results cancer. In addition, it was reported that inhibition of LARS may
indicate that cyclin D1, c-Myc, and vimentin might contribute to regulation of reduce cancer cell proliferation via the p21 signaling pathway and
cell proliferation and invasion by LARS. Further studies to investigate the cause apoptosis.
molecular network between c-Myc and LARS in human colorectal cancer Recently, many investigators have focused on LARS as a potential
cells are needed. target of anticancer agents. However, the role of LARS in colorectal
cancer are not clearly defined. Thus, we aimed to investigate the
This work was supported by the NRF funded by the Korean Government effect and molecular mechanism of LARS on cell proliferation,
(MSIP)(No. 2016R1A5A2007009). migration, and invasion in human colorectal cancer cells.
RESULTS

Figure 1. LARS overexpression enhances cell proliferation in Figure 3. Knockdown of LARS expression significantly decreased cell
human colorectal cancer SW480 cells. proliferation, migration and invasion of SW620 cell.

Figure 2. LARS overexpression increases migration and invasion Figure 4. The expression of cyclin D1, c-Myc, and vimentin in pCMV6-
in human colorectal cancer SW480 cells. SW480/LARS-SW480 and NC shRNA-SW620/LARS shRNA-SW620 cells.
CONCLUSION REFERENCES
Our data showed that LARS overexpression enhances cell proliferation, migration, and 1. Gao G, Yao Y, Li K, et al. A human leucyl-tRNA synthetase
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