Wild-Type IDH1 and Mutant IDH1 Opposingly Regulate Podoplanin Expression in Glioma

被引：18

作者：

Sun, Chao ^{[1
,2
,3
]}

Xiao, Liming ^{[1
,2
]}

Zhao, Yuanlin ^{[1
,2
]}

Shi, Jiankuan ^{[1
,2
,4
]}

Yuan, Yuan ^{[1
,2
]}

Gu, Yu ^{[1
,2
]}

Zhang, Feng ^{[1
,2
]}

Gao, Xing ^{[1
,2
]}

Yang, Ying ^{[1
,2
]}

Yang, Risheng ^{[1
,2
]}

Qin, Junhui ^{[1
,2
]}

Zhang, Jin ^{[1
,2
]}

Wang, Chao ^{[5
]}

Wang, Yingmei ^{[1
,2
]}

Wang, Zhe ^{[1
,2
]}

Hu, Peizhen ^{[1
,2
]}

Chang, Ting ^{[3
]}

Wang, Liang ^{[6
]}

Wang, Gang ^{[7
]}

Chen, Huangtao ^{[8
]}

Li, Zhuyi ^{[3
]}

Ye, Jing ^{[1
,2
,3
]}

机构：

[1] Fourth Mil Med Univ, Xijing Hosp, State Key Lab Canc Biol, Xian 710032, Peoples R China

[2] Fourth Mil Med Univ, Xijing Hosp, Dept Pathol, Xian 710032, Peoples R China

[3] Fourth Mil Med Univ, Tangdu Hosp, Dept Neurol, Xian 710032, Shaanxi, Peoples R China

[4] Int Med Ctr Hosp, Dept Neurol, Xian 710100, Peoples R China

[5] Chengdu Mil Gen Hosp, Dept Pathol, Chengdu 610083, Peoples R China

[6] Fourth Mil Med Univ, Tangdu Hosp, Dept Neurosurg, Xian 710032, Shaanxi, Peoples R China

[7] 74th Grp Army Hosp, Dept Gen Surg, Guangzhou 510318, Peoples R China

[8] Xi An Jiao Tong Univ, Hlth Sci Ctr, Xian 710061, Shaanxi, Peoples R China

来源：

TRANSLATIONAL ONCOLOGY | 2020年 / 13卷 / 04期

基金：

中国国家自然科学基金;

关键词：

ONCOMETABOLITE; 2-HYDROXYGLUTARATE; BRAIN-TUMORS; CLEC-2; CELLS; MUTATIONS; PHENOTYPE; ABSENCE; MARKER;

D O I：

10.1016/j.tranon.2020.100758

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Isocitrate dehydrogenase (IDH) mutations occur frequently in lower-grade gliomas, which result in genome-wide epigenetic alterations. The wild-type IDH1 is reported to participate in lipid biosynthesis and amino acid metabolism, but its role in tumorigenesis is still unclear. In this study, the expressions of IDH1 and podoplanin (Pdpn) were determined in IDH-mutated and IDH-wild-type gliomas, and their relationships in glioma were further analyzed. In addition, the regulation of wild-type IDH1 and mutant IDH1 on Pdpn expression was investigated by luciferase assays and promoter methylation analysis. Our study showed that Pdpn was almost undetectable in IDH-mutated glioma but strongly expressed in higher-grade IDH-wild-type glioma. Pdpn overexpression promoted the migration of glioma cells but had little effect on cell growth. Moreover, Pdpn expression was positively correlated with the increased wild-type IDH1 levels in IDH-wild-type glioma. Consistently, the wild-type IDH1 greatly promoted the transcription and expression of Pdpn, but the mutant IDH1 and D-2-hydroxyglutarate significantly suppressed Pdpn expression in glioma cells. Besides, our results revealed that the methylation of CpG islands in the Pdpn promoter was opposingly regulated by wild-type and mutant IDH1 in glioma. Collectively, our results indicated that wild-type and mutant IDH1 opposingly controlled the Pdpn expression in glioma by regulating its promoter methylation, which provides a basis for understanding the relationship between wild-type and mutant IDH1 in epigenetic regulation and tumorigenesis.

引用

页数：10

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