A novel prognostic factor TRIM44 promotes cell proliferation and migration and inhibits apoptosis in testicular germ cell tumors1

Tripartite motif 44 (TRIM44) is one of the TRIM family proteins that are involvedin ubiquitination and degradation of target proteins by modulating E3 ubiquitinligases. TRIM44 overexpression has been observed in various cancers. However,its association with testicular germ cell tumor (TGCT) is unknown. We aimed toinvestigate the clinical significance of TRIM44 and its function in TGCT. Highexpression of TRIM44 was significantly associated with a feto-protein levels, clinicalstage, nonseminomatous germ cell tumor (NSGCT), and cancer-specific survival(P = 0.0009, P = 0.0035, P = 0.0004, and P = 0.0140, respectively). Multivariateanalysis showed that positive TRIM44 IR was an independent predictor of cancerspecificmortality (P = 0.046). Gain-of-function study revealed that overexpressionof TRIM44 promoted cell proliferation and migration of NTERA2 and NEC8 cells.Knockdown of TRIM44 using siRNA promoted apoptosis and repressed cell proliferationand migration in these cells. Microarray analysis of NTERA2 cells revealedthat tumor suppressor genes such as CADM1, CDK19, and PRKACB were upregulatedin TRIM44-knockdown cells compared to control cells. In contrast, oncogenicgenes including C3AR1, ST3GAL5, and NT5E were downregulated in those cells.These results suggest that high expression of TRIM44 is associated with poorprognosis and that TRIM44 plays significant role in cell proliferation, migration,and anti-apoptosis in TGCT.