Abstract:

 Objective · To demonstrate the effect of TRIM59 on gliomagenesis and the molecular mechanism.  Methods · TRIM59 protein expression in glioma specimens was analyzed by immunohistochemical staining, and in several glioma cell lines by Western blotting and quantative PCR. After TRIM59 was knocked down by shRNAs, cell proliferation, migration, colony formation, and orthotopic xenograft brain tumor development were detected. The signaling pathway of TRIM59 in gliomas was also explored by RNA-Seq and KEGG PATHWAY analyses.  Results · The levels of TRIM59 protein expression in clinical glioma specimens were positively correlated with glioma malignancy. TRIM59 was highly expressed in LN229 and U87 glioma cells compared with normal human astrocytes. Knockdown of TRIM59 in these two cell lines with lentivirus-mediated shRNAs inhibited their proliferation, migration, and colony formation. Compared with the control xenograft models, knockdown of TRIM59 significantly inhibited glioma tumor growth. RNASeq and KEGG PATHWAY analyses identified that TRIM59 knockdown down-regulated 306 genes, among which PI3K/AKT signal pathway-related genes were the most. Moreover, TRIM59 knockdown suppressed AKT phosphorylation, whereas overexpression of a constitutively actived AKT (Myr-AKT) rescued TRIM59 knockdown-inhibited cell proliferation.  Conclusion · TRIM59 is a new glioma oncogene, which may take effect through activating PI3K/ AKT signaling pathway.

Key words: TRIM59, glioma, PI3K/AKT signaling pathway, oncogene