Open AccessTripartite Motif-Containing 46 Promotes Viability and Inhibits Apoptosis of Osteosarcoma Cells by Activating NF-B Signaling Through Ubiquitination of PPAR
Author(s) -
Weihang Jiang,
Xinyu Cai,
Tianyang Xu,
Kaiyuan Liu,
Dong Yang,
Lin Fan,
Guodong Li,
Yu Xiao
Publication year - 2020
Publication title -
oncology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 57
eISSN - 1555-3906
pISSN - 0965-0407
DOI - 10.3727/096504020x15868639303417
Subject(s) - pyrrolidine dithiocarbamate , gene knockdown , cancer research , oncogene , apoptosis , signal transduction , carcinogenesis , nf κb , viability assay , biology , cell growth , nfkb1 , cell cycle , ubiquitin , iκbα , osteosarcoma , ubiquitin ligase , transcription factor , microbiology and biotechnology , cancer , biochemistry , genetics , gene
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, Ennekings 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.