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To identify potential therapeutic targets for lung cancer, we performed semi‐genome‐wide sh RNA  screening combined with the utilization of genome‐wide expression and copy number data. sh RNA  screening targeting 5043 genes in  NCI ‐H460 identified 51 genes as candidates. Pathway analysis revealed that the 51 genes were enriched for the five pathways, including ribosome, proteasome,  RNA  polymerase, pyrimidine metabolism and spliceosome pathways. We focused on the proteasome pathway that involved six candidate genes because its activation has been demonstrated in diverse human malignancies, including lung cancer. Microarray expression and array  CGH  data showed that   PSMA 6 , a proteasomal subunit of a 20S catalytic core complex, was highly expressed in lung cancer cell lines, with recurrent gene amplifications in some cases. Therefore, we further examined the roles of   PSMA 6  in lung cancer. Silencing of   PSMA 6  induced apoptosis or G2/M cell cycle arrest in cancer cell lines but not in an immortalized normal lung cell line. These results suggested that   PSMA 6  serves as an attractive target with a high therapeutic index for lung cancer.

Identification of proteasomal catalytic subunit PSMA 6 as a therapeutic target for lung cancer