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Ubiquilin 2 enhances osteosarcoma progression through resistance to hypoxic stress.
- Source :
-
Oncology reports [Oncol Rep] 2015 Apr; Vol. 33 (4), pp. 1799-806. Date of Electronic Publication: 2015 Feb 09. - Publication Year :
- 2015
-
Abstract
- Ubiquilin 2 (UBQLN2), a member of the ubiquitin-like protein family (ubiquilins), maintains protein homeostasis. Although UBQLN2 has been implicated in the pathogenesis of neurodegenerative diseases, it is also associated with malignant tumors. Therefore, we examined whether UBQLN2 plays a role in human osteosarcoma. The human osteosarcoma cell line MG63 was transfected with UBQLN2 siRNA and cultured under hypoxic conditions. The rat osteosarcoma cell line COS1NR was inoculated into Fischer 344 rats, followed by injection of UBQLN2 siRNA with atelocollagen. An immunohistochemical analysis of UBQLN2 was performed using 34 cases of human high-grade osteosarcomas, and metastasis-free survival was estimated by the Kaplan-Meier method. Silencing of UBQLN2 by siRNA transfection under hypoxia led to activation of JNK and p38, resulting in induction of apoptosis in the osteosarcoma cell line MG63. Injection of UBQLN2 siRNA suppressed tumor growth in the rat osteosarcoma model, followed by apoptosis induction. The immunohistochemical examination revealed that high UBQLN2 expression was significantly associated with the unfavorable metastasis-free survival of osteosarcoma patients. UBQLN2 plays an important role in resistance to hypoxic stress and enhances tumor progression in osteosarcoma. UBQLN2 may be a new molecular target for chemotherapeutics and a useful clinicopathological marker in human osteosarcoma.
- Subjects :
- Adaptor Proteins, Signal Transducing
Animals
Apoptosis
Autophagy-Related Proteins
Blotting, Western
Bone Neoplasms genetics
Bone Neoplasms metabolism
Cell Line, Tumor
Disease Progression
JNK Mitogen-Activated Protein Kinases metabolism
Osteosarcoma genetics
Osteosarcoma metabolism
RNA, Small Interfering genetics
Rats
Rats, Inbred F344
Real-Time Polymerase Chain Reaction
Transfection methods
p38 Mitogen-Activated Protein Kinases metabolism
Bone Neoplasms physiopathology
Cell Cycle Proteins physiology
Hypoxia metabolism
Osteosarcoma physiopathology
Ubiquitins physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1791-2431
- Volume :
- 33
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Oncology reports
- Publication Type :
- Academic Journal
- Accession number :
- 25672654
- Full Text :
- https://doi.org/10.3892/or.2015.3788