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Fragile X mental retardation protein promotes astrocytoma proliferation via the MEK/ERK signaling pathway.


ABSTRACT:

Objective

To examine the association between fragile X mental retardation protein (FMRP) expression and astrocytoma characteristics.

Methods

Pathologic grade and expressions of glial fibrillary acidic protein (GFAP), Ki67 (proliferation marker), and FMRP were determined in astrocytoma specimens from 74 patients. Kaplan-Meier survival analysis was undertaken. Pathologic grade and protein levels of FMRP were determined in 24 additional patients with astrocytoma and 6 controls (cerebral trauma). In cultured U251 and U87 cell lines, the effects of FMRP knock-down on cell proliferation, AKT/mTOR/GSK-3? and MEK/ERK signaling were studied. The effects of FMRP knock-down on the volumes and weights of U251 cell-derived orthotopic tumors in mice were investigated.

Results

In patients, FMRP expression was increased in grade IV (5.1-fold, P<0.01) and grade III (3.2-fold, P<0.05) astrocytoma, compared with controls. FMRP and Ki67 expressions were positively correlated (R2=0.877, P<0.001). Up-regulation of FMRP was associated with poorer survival among patients with FMRP integrated optical density >30 (P<0.01). In astrocytoma cell lines, FMRP knock-down slowed proliferation (P<0.05), inhibited total MEK levels P<0.05, and reduced phosphorylation of MEK (Ser217/221) and ERK (Thr202/Tyr204) (P<0.05). In mice with orthotopic tumors, FMRP knock-down decreased FMRP and Ki67 expressions, and reduced tumor volume and weight (36.3% or 61.5% on day 15, both P<0.01). Also, phosphorylation of MEK (Ser217/221) and ERK (Thr202/Tyr204), and total MEK in xenografts were decreased in sh-FMRP xenografts compared with non-transfected ones (all P<0.05).

Conclusion

Enhanced FMRP expression in astrocytoma may promote proliferation through activation of MEK/ERK signaling.

SUBMITTER: Xing Z 

PROVIDER: S-EPMC5342749 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Publications

Fragile X mental retardation protein promotes astrocytoma proliferation via the MEK/ERK signaling pathway.

Xing Zhou Z   Zeng Minling M   Hu Huixian H   Zhang Hui H   Hao Zhuofang Z   Long Yuesheng Y   Chen Shengqiang S   Su Hang H   Yuan Zhongmin Z   Xu Meng M   Chen Jingqi J  

Oncotarget 20161101 46


<h4>Objective</h4>To examine the association between fragile X mental retardation protein (FMRP) expression and astrocytoma characteristics.<h4>Methods</h4>Pathologic grade and expressions of glial fibrillary acidic protein (GFAP), Ki67 (proliferation marker), and FMRP were determined in astrocytoma specimens from 74 patients. Kaplan-Meier survival analysis was undertaken. Pathologic grade and protein levels of FMRP were determined in 24 additional patients with astrocytoma and 6 controls (cereb  ...[more]

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