title: PSMC2 is up-regulated in osteosarcoma and regulates osteosarcoma cell proliferation, apoptosis and migration.
abstract: Proteasome 26S subunit ATPase 2 (PSMC2) is a recently identified gene potentially associated with certain human carcinogenesis. However, the expressional correlation and functional importance of PSMC2 in osteosarcoma is still unclear. Current study was focused on elucidating the significance of PSMC2 on malignant behaviors in osteosarcoma including proliferation, apoptosis, colony formation, migration as well as invasion. The high protein levels of PSMC2 in osteosarcoma samples were identified by tissue microarrays analysis. Besides, its expression in the levels of mRNA and protein was also detected in four different osteosarcoma cell lines by real-time PCR and western blotting separately. Silencing PSMC2 by RNA interference in osteosarcoma cell lines (SaoS-2 and MG-63) would significantly suppress cell proliferation, enhance apoptosis, accelerate G2/M phase and/or S phase arrest, and decrease single cell colony formation. Similarly, pharmaceutical inhibition of proteasome with MG132 would mimic the PSMC2 depletion induced defects in cell cycle arrest, apoptosis and colonies formation. Silencing of PSMC2 was able to inhibit osteosarcoma cell motility, invasion as well as tumorigenicity in nude mice. Moreover, the gene microarray indicated knockdown of PSMC2 notably changed a number of genes, especially some cancer related genes including ITGA6, FN1, CCND1, CCNE2 and TGFβR2, and whose expression changes were further confirmed by western blotting. Our data suggested that PSMC2 may work as an oncogene for osteosarcoma and that inhibition of PSMC2 may be a therapeutic strategy for osteosarcoma treatment.
authors.affiliation: Department of Orthopaedics, The First Affiliated Hospital of Dalian Medical University, 116011, Dalian, Liaoning, People's Republic of China.|Department of Orthopaedics, The Third Affiliated Hospital of Dalian Medical University, 116200, Jinpu New Area, Liaoning, People's Republic of China.
authors.forename: Mingzhi
authors.initials: M
authors.lastname: Song
authors.affiliation: Department of Orthopaedics, Affiliated Central Hospital of Shenyang Medical College, 110024, Shenyang, Liaoning, People's Republic of China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Orthopaedics, The First Affiliated Hospital of Dalian Medical University, 116011, Dalian, Liaoning, People's Republic of China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Orthopaedics, The First Affiliated Hospital of Dalian Medical University, 116011, Dalian, Liaoning, People's Republic of China.
authors.forename: Shouyu
authors.initials: S
authors.lastname: Wang
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities / Q000235:genetics* / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001859:Bone Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D064593:Heterografts; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D009367:Neoplasm Staging; D012516:Osteosarcoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D046988:Proteasome Endopeptidase Complex / Q000235:genetics* / Q000378:metabolism; D061988:Proteasome Inhibitors / Q000494:pharmacology; D034622:RNA Interference; D015398:Signal Transduction / Q000187:drug effects; D055815:Young Adult
chemical_list: D061988:Proteasome Inhibitors; C075363:PSMC2 protein, human; D046988:Proteasome Endopeptidase Complex; D000074183:ATPases Associated with Diverse Cellular Activities
keywords: PSMC2; carcinogenesis; oncogenes; osteosarcoma