Abstract
Background: RPS15A (Ribosomal Protein S15A) promotes mRNA/ribosome interactions in translation. It is critical for the process of eukaryotic protein biosynthesis. Recently, aberrantly expressed RPS15A was found in the hepatitis virus and in malignant tumors. However, the role of RPS15A has not been fully revealed on the development of lung cancer. Method: In this study, a Tissue Microarray (TMA) of primary lung adenocarcinoma tissue specimens was carried out. Furthermore, to further investigate the function of RPS15A in lung cancer, RPS15A-specific short hairpin RNA (shRNA) expressing lentivirus (Lv-shRPS15A) was constructed and used to infect H1299 and A549 cells. Result: Our data showed that RPS15A expression was increased in tumor tissues. Furthermore, the knockdown of RSP15A inhibited cancer cell growth and induced apoptosis in the cancer cells. Gene expression profile microarray also revealed that the P53 signaling pathway was activated in Lv-shRPS15A-infected cancer cells. Conclusion: Taken together, our results demonstrate that RPS15A is a novel oncogene in non-small cell lung cancer and may be a potential therapeutic target in lung cancer.
Highlights
Lung cancer is the most prevalent of malignant tumors and the leading cause of cancerrelated death in the world (Jemal et al, 2011)
G1/S cell cycle phase arrest induced by cdc33 mutation could be reversed by Ribosomal Protein S15a (RPS15A) over-expression, these findings suggest that RPS15A may play a role in cell cycle transition (Lavoie et al, 1994)
RPS15A was significantly overexpressed in lung adenocarcinoma tissues We detected the expression of RPS15A protein in a tissue microarray (TMA) of primary lung adenocarcinoma and adjacent normal lung tissue specimens using immunohistochemical staining with an anti-RPS15A antibody
Summary
Lung cancer is the most prevalent of malignant tumors and the leading cause of cancerrelated death in the world (Jemal et al, 2011). Tumorigenesis involves multistep development to acquire certain malignant capabilities, such as sustaining proliferative signaling, resisting cell apoptosis, activating invasion and metastasis et al (Hanahan & Weinberg, 2011) Underlying these abilities of tumor cells, rapid de novo biosynthesis of functional ribosome is essential for cancer. Human Ribosomal Protein S15a (RPS15A) is a highly conserved cellular gene that maps to human chromosome 16p12.3 locus (Chan et al, 1994; Schaap et al, 1995) It promotes mRNA/ribosome binding in translation via the interactions with the capbinding subunit of eukaryotic initiation factor 4F (eIF-4F) (Linder & Prat, 1990). To examine its functional role in lung cancer progress, an RPS15A-specific small interfering RNA (siRNA)-lentiviral vector was constructed to block RPS15A expression in human lung adenocarcinoma H1299 and A549 cells. To further explore the potential molecular mechanisms, we performed a human whole genome oligo microarray followed by a KEGG pathway enrichment analysis
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