Open Access
ARTICLE
Tripartite Motif-Containing 46 Promotes Viability and Inhibits Apoptosis of Osteosarcoma Cells by Activating NF-kB Signaling Through Ubiquitination of PPARα
Wenwei Jiang*, Xinyu Cai*, Tianyang Xu*, Kaiyuan Liu*, Dong Yang*, Lin Fan*, Guodong Li*, Xiao Yu†
* Department of Orthopedics, Shanghai Tenth People’s Hospital, Tong Ji University School of Medicine, Shanghai, P.R. China
† Department of Orthopedics, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital,
Suzhou, P.R. China
Oncology Research 2020, 28(4), 409-421. https://doi.org/10.3727/096504020X15868639303417
Abstract
Osteosarcoma (OS), the most common bone cancer, causes high morbidity in children and young adults.
TRIM46 is a member of the family of tripartite motif (TRIM)-containing proteins that serve as important regulators of tumorigenesis. Here we investigate the possible role of TRIM46 in OS and the underlying molecular
mechanism. We report an increase in the expression of TRIM46 in OS and its association with tumor size,
Enneking’s stage, and patient prognosis. TRIM46 knockdown inhibits OS cell viability and cell cycle progression and induces apoptosis, while TRIM46 overexpression exerts inverse effects, which are inhibited by peroxisome proliferator-activated receptor alpha (PPAR ) overexpression and the nuclear factor kappa B (NF- B)
inhibitor, pyrrolidine dithiocarbamate (PDTC). Furthermore, TRIM46 negatively regulates PPAR expression via ubiquitination-mediated protein degradation and modification. PPAR overexpression also inactivates NF- B signaling and NF- B promoter activity in OS cells overexpressing TRIM46. Moreover, TRIM46
knockdown inhibits tumor growth and induces apoptosis of OS cells in vivo. TRIM46 acts as an oncogene in
OS by interacting with and ubiquitinating PPAR , resulting in the activation of NF- B signaling pathway.
Thus, TRIM46 may be a potential biomarker of carcinogenesis.
Key words: Osteosarcoma (OS); TRIM46; Ubiquitination; NF
Keywords
Cite This Article
APA Style
Jiang, W., Cai, X., Xu, T., Liu, K., Yang, D. et al. (2020). Tripartite motif-containing 46 promotes viability and inhibits apoptosis of osteosarcoma cells by activating nf-kb signaling through ubiquitination of PPARα. Oncology Research, 28(4), 409-421. https://doi.org/10.3727/096504020X15868639303417
Vancouver Style
Jiang W, Cai X, Xu T, Liu K, Yang D, Fan L, et al. Tripartite motif-containing 46 promotes viability and inhibits apoptosis of osteosarcoma cells by activating nf-kb signaling through ubiquitination of PPARα. Oncol Res. 2020;28(4):409-421 https://doi.org/10.3727/096504020X15868639303417
IEEE Style
W. Jiang et al., "Tripartite Motif-Containing 46 Promotes Viability and Inhibits Apoptosis of Osteosarcoma Cells by Activating NF-kB Signaling Through Ubiquitination of PPARα," Oncol. Res., vol. 28, no. 4, pp. 409-421. 2020. https://doi.org/10.3727/096504020X15868639303417