Identification of proteasomal catalytic subunit PSMA6 as a therapeutic target for lung cancer
| العنوان: | Identification of proteasomal catalytic subunit PSMA6 as a therapeutic target for lung cancer |
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| المؤلفون: | Masashi Kondo, Tomohiko Kakumu, Kohei Yokoi, Yoshitaka Sekido, Tetsunari Hase, Naoyuki Yogo, Lauren Averett Byers, John V. Heymach, John D. Minna, Mitsuo Sato, Masahiro Morise, Toshio Kato, Luc Girard, Yoshinori Hasegawa, Kevin R. Coombes, Daiki Goto, Takayuki Fukui |
| المصدر: | Cancer Science |
| بيانات النشر: | John Wiley and Sons Inc., 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, Male, Cancer Research, Candidate gene, Spliceosome, Proteasome Endopeptidase Complex, Lung Neoplasms, Cell Survival, Blotting, Western, PSMA6, Apoptosis, Kaplan-Meier Estimate, Biology, Cell Line, Small hairpin RNA, 03 medical and health sciences, Cell, Molecular, and Stem Cell Biology, Carcinoma, Non-Small-Cell Lung, Catalytic Domain, Cell Line, Tumor, medicine, Gene silencing, Humans, Molecular Targeted Therapy, Lung cancer, Gene, Aged, Cell Proliferation, spliceosomes, Reverse Transcriptase Polymerase Chain Reaction, Gene Expression Profiling, Gene Amplification, General Medicine, Original Articles, medicine.disease, small interfering RNA, Immunohistochemistry, 3. Good health, G2 Phase Cell Cycle Checkpoints, Gene Expression Regulation, Neoplastic, 030104 developmental biology, Oncology, Proteasome, A549 Cells, Cancer research, Original Article, Female, RNA Interference, Signal Transduction |
| الوصف: | To identify potential therapeutic targets for lung cancer, we performed semi-genome-wide shRNA screening combined with the utilization of genome-wide expression and copy number data. shRNA 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 PSMA6, 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 PSMA6 in lung cancer. Silencing of PSMA6 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 PSMA6 serves as an attractive target with a high therapeutic index for lung cancer. |
| اللغة: | English |
| تدمد: | 1349-7006 1347-9032 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1335c5aa1034bcb4c332b5defe96c6eeTest http://europepmc.org/articles/PMC5406588Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....1335c5aa1034bcb4c332b5defe96c6ee |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 13497006 13479032 |
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