title: Downregulation of HTATIP2 expression is associated with promoter methylation and poor prognosis in glioma.
abstract: Glioma is an aggressive tumor with poor prognosis. Identification of precise prognostic marker and effective therapeutic target is important in the treatment of glioma. HTATIP2 is a novel tumor suppressor gene, which is frequently silenced by epigenetic mechanisms in many caners. However, the expression of HTATIP2 and how it is regulated in glioma are unknown. Hence, we assessed whether loss of HTATIP2 expression occurs in glioma, and, if so, what is the mechanism of such loss. We found that HTATIP2 expression was absent or diminished in primary gliomas compared with normal brain tissue. In vitro experiments showed that HTATIP2 expression could be restored via 5-aza-2'deoxycytidine treatment in U87 and U251 cell lines. Methyl-specific PCR indicated that the two cell lines and 60% primary gliomas carried aberrant methylated HTATIP2 alleles while normal brain tissue did not. Pyrosequencing confirmed these results and showed a higher density of methylation in the minimal promoter element, which contains four Sp1 binding sites in primary gliomas, than in normal brain tissue. Finally, we found that the overall survival was significantly higher in patients with positive HTATIP2 expression than those with loss of HTATIP2 expression. Overexpression of HTATIP2 inhibited glioma proliferation and growth in vitro. Taken together, the present study showed that loss of HTATIP2 expression was a frequent event in glioma and is associated with poor prognosis. Promoter methylation may be an underlying mechanism.
authors.affiliation: Affiliated Bayi Brain Hospital, Bayi Clinical College, Southern Medical University, Beijing, People's Republic of China.
authors.forename: Xingyu
authors.initials: X
authors.lastname: Dong
authors.affiliation: Affiliated Bayi Brain Hospital, Bayi Clinical College, Southern Medical University, Beijing, People's Republic of China.
authors.forename: Qingshan
authors.initials: Q
authors.lastname: Deng
authors.affiliation: Affiliated Bayi Brain Hospital, Bayi Clinical College, Southern Medical University, Beijing, People's Republic of China.
authors.forename: Xiaohu
authors.initials: X
authors.lastname: Nie
authors.affiliation: Affiliated Bayi Brain Hospital, Bayi Clinical College, Southern Medical University, Beijing, People's Republic of China.
authors.forename: Maoying
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Affiliated Bayi Brain Hospital, Bayi Clinical College, Southern Medical University, Beijing, People's Republic of China.
authors.forename: Weiqiang
authors.initials: W
authors.lastname: Jia
authors.affiliation: Affiliated Bayi Brain Hospital, General Hospital of Beijing Military Region, Beijing, People's Republic of China.
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Pathology, General Hospital of Beijing Military Region, Beijing, People's Republic of China.
authors.forename: Chunwei
authors.initials: C
authors.lastname: Xu
authors.affiliation: Affiliated Bayi Brain Hospital, Bayi Clinical College, Southern Medical University, Beijing, People's Republic of China. Electronic address: xuruxiang81nk@163.com.
authors.forename: Ruxiang
authors.initials: R
authors.lastname: Xu
mesh_terms: D000123:Acetyltransferases / Q000096:biosynthesis*; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D001665:Binding Sites; D001932:Brain Neoplasms / Q000235:genetics* / Q000401:mortality; D045744:Cell Line, Tumor; D019175:DNA Methylation / Q000235:genetics*; D000077209:Decitabine; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000235:genetics* / Q000401:mortality; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics*; D016329:Sp1 Transcription Factor / Q000378:metabolism; D014157:Transcription Factors / Q000096:biosynthesis*
chemical_list: D000964:Antimetabolites, Antineoplastic; D016329:Sp1 Transcription Factor; D014157:Transcription Factors; D000077209:Decitabine; D000123:Acetyltransferases; C111246:HTATIP2 protein, human; D001374:Azacitidine
keywords: Glioma; HTATIP2; Methylation; Prognosis