High Expression of Pirh2 is Associated with Poor Prognosis in Glioma.

Abstract

p53-induced protein with a RING-H2 domain (Pirh2), also known as Rchy1, is an ubiquitin E3 ligase that regulates the turnover and functionality of several proteins involved in cell proliferation and differentiation, cell cycle checkpoints, and cell death. However, it remains unclear whether aberrant expression of Pirh2 is involved in the development of glioma, a major type of primary brain tumor in adults. Western blot and immunohistochemical analyses showed that Pirh2 was highly expressed in glioma specimens, compared with normal brain tissues. High Pirh2 expression was positively correlated with higher tumor grade, as well as Ki-67 expression. Kaplan-Meier analysis revealed that patients with high Pirh2 expression had worsened prognosis, compared with those with low Pirh2 expression. Moreover, to determine whether Pirh2 could regulate malignant behavior of glioma cells, we transfected glioma cells with interfering RNA targeting Pirh2 to specifically silence Pirh2 expression. Mechanistically, our results indicated that knockdown of Pirh2 induced the apoptosis of glioma cells. In addition, depletion of Pirh2 diminished the expression of PCNA and cyclin D1 and led to cell cycle arrest at G1 phase. Taken together, these findings for the first time suggest that Pirh2 might play an important role in the regulation of glioma proliferation and apoptosis and thus serve as a promising therapeutic target in the treatment of glioma.