Abstract
Molecular mechanism of lung carcinogenesis and its aggressive nature is still largely elusive. To uncover the biomarkers related with tumorigenesis and behavior of lung cancer, we screened novel differentially expressed genes (DEG) in A549 lung cancer cell line by comparison with CCD-25Lu, normal pulmonary epithelial cell line, using annealing control primer(ACP)-based GeneFishing system. Of the DEGs, over-expression of leucyl-tRNA synthetase 1 (LARS1) was prominent and this up-regulation was confirmed by immunoblotting and real-time quantitative RT-PCR analysis. In addition to A549 cell line, primary lung cancer tissues also expressed higher level of LARS1 mRNA than their normal counter tissues. To explore the oncogenic potential of LARS1 over-expression in lung cancer, we knocked-down LARS1 by treating siRNA and observed the tumor behavior. LARS1 knock-down cells showed reduced ability to migrate through transwell membrane and to form colonies in both soft agar and culture plate. Taken together, these findings suggest that LARS1 may play roles in migration and growth of lung cancer cells, which suggest its potential implication in lung tumorigenesis.
Highlights
Lung cancer is the most common and the leading cause of cancer death in the world (Boyle and Ferlay, 2005)
We suggest that leucyl-tRNA synthetase 1 (LARS1), a member of aminoacyl-tRNA synthetase (ARS) family, involves in lung tumorigenesis and tumor cell behavior by influencing tumor cell growth and migration
Consistent up-regulation of LARS1 in both differentially expressed genes (DEG) and quantitative RT-PCR (qRT-PCR) shows the reliability of annealing control primers (ACP)-based GeneFishing analysis, which we employed in this study
Summary
Lung cancer is the most common and the leading cause of cancer death in the world (Boyle and Ferlay, 2005). Carcinoembryonic antigen (CEA) (Okada et al, 2004), CYFRA 21-1 (Kulpa et al, 2002), neuron-specific enolase (NSE) (Ferrigino et al, 2003), squamous cell carcinoma (SCC) antigen (Schneider, 2006), tumor M2-pyruvate kinase (Tumor M2-PK) (Schneider, 2006) and c-reactive protein (CRP) (Siemes, et al, 2006) have been well studied Genomic aberrations are another frequently observed event in lung cancer (Testa et al, 1997; Balsara and Testa, 2002). Novel cancer related genes have been identified in the recurrently altered genomic regions in lung cancers by using whole-genome copy number analysis methods such as array-comparative genomic hybridization (array-CGH) (Kim et al, 2005). We observed the expression profile of LARS1 in primary lung cancer samples
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