title: A novel prognostic factor TRIM44 promotes cell proliferation and migration, and inhibits apoptosis in testicular germ cell tumor.
abstract: Tripartite motif 44 (TRIM44) is one of the TRIM family proteins that are involved in ubiquitination and degradation of target proteins by modulating E3 ubiquitin ligases. TRIM44 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 TRIM44 and its function in TGCT. High expression of TRIM44 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 TRIM44 IR was an independent predictor of cancer-specific mortality (P = 0.046). Gain-of-function study revealed that overexpression of TRIM44 promoted cell proliferation and migration of NTERA2 and NEC8 cells. Knockdown of TRIM44 using siRNA promoted apoptosis and repressed cell proliferation and migration in these cells. Microarray analysis of NTERA2 cells revealed that tumor suppressor genes such as CADM1, CDK19, and PRKACB were upregulated in TRIM44-knockdown cells compared to control cells. In contrast, oncogenic genes including C3AR1, ST3GAL5, and NT5E were downregulated in those cells. These results suggest that high expression of TRIM44 is associated with poor prognosis and that TRIM44 plays significant role in cell proliferation, migration, and anti-apoptosis in TGCT.
authors.affiliation: Department of Urology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.|Department of Geriatric Medicine and Anti-Aging Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Yuta
authors.initials: Y
authors.lastname: Yamada
authors.affiliation: Department of Geriatric Medicine and Anti-Aging Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.|Functional Biogerontology, Tokyo Metropolitan Institute of Gerontology, Itabashi-ku, Tokyo, Japan.
authors.forename: Ken-Ichi
authors.initials: KI
authors.lastname: Takayama
authors.affiliation: Department of Urology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Fujimura
authors.affiliation: Department of Geriatric Medicine and Anti-Aging Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.|Urology, Nihon University School of Medicine, Itabashi-ku, Japan.
authors.forename: Daisaku
authors.initials: D
authors.lastname: Ashikari
authors.affiliation: Department of Geriatric Medicine and Anti-Aging Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.|Urology, Nihon University School of Medicine, Itabashi-ku, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Obinata
authors.affiliation: Urology, Nihon University School of Medicine, Itabashi-ku, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Takahashi
authors.affiliation: Division of Gene Regulation and Signal Transduction, Research Center of Genomic Medicine, Saitama Medical University, Saitama, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Ikeda
authors.affiliation: Department of Urology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Shigenori
authors.initials: S
authors.lastname: Kakutani
authors.affiliation: Department of Geriatric Medicine and Anti-Aging Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Urano
authors.affiliation: Department of Urology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Fukuhara
authors.affiliation: Department of Urology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Homma
authors.affiliation: Department of Geriatric Medicine and Anti-Aging Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.|Functional Biogerontology, Tokyo Metropolitan Institute of Gerontology, Itabashi-ku, Tokyo, Japan.|Division of Gene Regulation and Signal Transduction, Research Center of Genomic Medicine, Saitama Medical University, Saitama, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Inoue
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D009373:Neoplasms, Germ Cell and Embryonal / Q000378:metabolism* / Q000473:pathology*; D009857:Oncogenes / Q000235:genetics; D011379:Prognosis; D013736:Testicular Neoplasms / Q000378:metabolism* / Q000473:pathology*; D000070584:Tripartite Motif Proteins
chemical_list: D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; C540677:TRIM44 protein, human; D000070584:Tripartite Motif Proteins
keywords: Apoptosis; TRIM family; immunohistochemistry; microarray; testicular germ cell tumor