E2F7-EZH2 axis regulates PTEN/AKT/mTOR signalling and glioblastoma progression

被引：91

作者：

Yang, Rui ^{[1
,2
]}

Wang, Mei ^{[2
,3
]}

Zhang, Guanghui ^{[2
,4
]}

Bao, Yonghua ^{[1
]}

Wu, Yanan ^{[2
,4
]}

Li, Xiuxiu ^{[5
]}

Yang, Wancai ^{[1
,6
]}

Cui, Hongjuan ^{[2
,4
]}

机构：

[1] Jining Med Univ, Inst Precis Med, Key Lab Precis Oncol Shandong Higher Educ, Jining, Peoples R China

[2] Southwest Univ, State Key Lab Silkworm Genome Biol, Chongqing, Peoples R China

[3] Zunyi Med Univ, Guizhou Prov Coll, Based Key Lab Tumor Prevent & Treatment Distinct, Zunyi, Guizhou, Peoples R China

[4] Southwest Univ, Canc Ctr, Engn Res Ctr Canc Biomed & Translat Med, Med Res Inst, Chongqing, Peoples R China

[5] Second Peoples Hosp Liaocheng, Dept Pharm, Liaocheng, Shandong, Peoples R China

[6] Univ Illinois, Dept Pathol, Chicago, IL USA

来源：

BRITISH JOURNAL OF CANCER | 2020年 / 123卷 / 09期

基金：

中国国家自然科学基金;

关键词：

GROUP PROTEIN EZH2; E2F FAMILY-MEMBER; CELL-PROLIFERATION; ACTIVATION; REPRESSION; PATHWAY; GROWTH; EXPRESSION; CHEMOKINES; ROLES;

D O I：

10.1038/s41416-020-01032-y

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background E2F transcription factors are considered to be important drivers of tumour growth. E2F7 is an atypical E2F factor, and its role in glioblastoma remains undefined. Methods E2F7 expression was examined in patients by IHC and qRT-PCR. The overall survival probability was determined by statistical analyses. MTT assay, colony formation, cell-cycle assay, cell metastasis and the in vivo model were employed to determine the functional role of E2F7 in glioblastoma. Chromatin immunoprecipitation, luciferase assay and western blot were used to explore the underlying mechanisms. Results E2F7 was found to be up-regulated in glioblastoma patients, and high E2F7 expression was associated with poor overall survival in glioblastoma patients. Functional studies showed that E2F7 promoted cell proliferation, cell-cycle progression, cell metastasis and tumorigenicity abilities in vitro and in vivo. E2F7 promoted the transcription of EZH2 by binding to its promoter and increased H3K27me3 level. EZH2 recruited H3K27me3 to the promoter of PTEN and inhibited PTEN expression, and then activated the AKT/mTOR signalling pathway. In addition, restored expression of EZH2 recovered the abilities of cell proliferation and metastasis in E2F7-silencing cells. Conclusion Collectively, our findings indicate that E2F7 promotes cell proliferation, cell metastasis and tumorigenesis via EZH2-mediated PTEN/AKT/mTOR pathway in glioblastoma.

引用

页码：1445 / 1455

页数：11