title: 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.
authors.affiliation: Department of Neurosurgery, The Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong, 226001, People's Republic of China.
authors.forename: Yifeng
authors.initials: Y
authors.lastname: Bao
authors.affiliation: Department of Endocrinology, The Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong, 226001, People's Republic of China.
authors.forename: Xue
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Neurosurgery, The Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong, 226001, People's Republic of China.
authors.forename: Debin
authors.initials: D
authors.lastname: Yuan
authors.affiliation: Department of Neurosurgery, The Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong, 226001, People's Republic of China. ntshiwei123@163.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Shi
authors.affiliation: Department of Neurosurgery, The Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong, 226001, People's Republic of China. chengjinluo@163.com.
authors.forename: Jinlong
authors.initials: J
authors.lastname: Shi
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D015996:Survival Rate / Q000639:trends; D044767:Ubiquitin-Protein Ligases / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; C485369:RCHY1 protein, human; D044767:Ubiquitin-Protein Ligases
keywords: Apoptosis; Glioma; Pirh2; Proliferation