Open AccessA novel prognostic factor TRIM44 promotes cell proliferation and migration, and inhibits apoptosis in testicular germ cell tumor
Author(s) -
Yamada Yuta,
Takayama Kenichi,
Fujimura Tetsuya,
Ashikari Daisaku,
Obinata Daisuke,
Takahashi Satoru,
Ikeda Kazuhiro,
Kakutani Shigenori,
Urano Tomohiko,
Fukuhara Hiroshi,
Homma Yukio,
Inoue Satoshi
Publication year - 2017
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13105
Subject(s) - gene knockdown , cancer research , trim , cell growth , apoptosis , biology , downregulation and upregulation , cancer , medicine , gene , genetics , computer science , operating system
Tripartite motif 44 ( TRIM 44) is one of the TRIM family proteins that are involved in ubiquitination and degradation of target proteins by modulating E3 ubiquitin ligases. TRIM 44 overexpression has been observed in various cancers. However, its association with testicular germ cell tumor ( TGCT ) is unknown. We aimed to investigate the clinical significance of TRIM 44 and its function in TGCT . High expression of TRIM 44 was significantly associated with α feto‐protein levels, clinical stage, nonseminomatous germ cell tumor ( NSGCT ), and cancer‐specific survival ( P = 0.0009, P = 0.0035, P = 0.0004, and P = 0.0140, respectively). Multivariate analysis showed that positive TRIM 44 IR was an independent predictor of cancer‐specific mortality ( P = 0.046). Gain‐of‐function study revealed that overexpression of TRIM 44 promoted cell proliferation and migration of NTERA 2 and NEC 8 cells. Knockdown of TRIM 44 using si RNA promoted apoptosis and repressed cell proliferation and migration in these cells. Microarray analysis of NTERA 2 cells revealed that tumor suppressor genes such as CADM 1 , CDK 19 , and PRKACB were upregulated in TRIM 44‐knockdown cells compared to control cells. In contrast, oncogenic genes including C3 AR 1 , ST 3 GAL 5 , and NT 5E were downregulated in those cells. These results suggest that high expression of TRIM 44 is associated with poor prognosis and that TRIM 44 plays significant role in cell proliferation, migration, and anti‐apoptosis in TGCT .