Fragile X mental retardation protein promotes astrocytoma proliferation via the MEK/ERK signaling pathway.
To examine the association between fragile X mental retardation protein (FMRP) expression and astrocytoma characteristics.



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-3β 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.



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).



Enhanced FMRP expression in astrocytoma may promote proliferation through activation of MEK/ERK signaling.
Department of Oncology, The First Affiliated Hospital, Jinan University, Guangzhou 510632, People's Republic of China.|Department of Neurosurgery, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, People's Republic of China.
Zhou
Z
Xing
Department of Neurosurgery, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, People's Republic of China.
Minling
M
Zeng
Translational Medicine Center, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, People's Republic of China.
Huixian
H
Hu
Translational Medicine Center, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, People's Republic of China.
Hui
H
Zhang
Department of Pathology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, People's Republic of China.
Zhuofang
Z
Hao
Institute of Neuroscience, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and Ministry of Education of China, Guangzhou Medical University, Guangzhou 510260, People's Republic of China.
Yuesheng
Y
Long
Institute of Neuroscience, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and Ministry of Education of China, Guangzhou Medical University, Guangzhou 510260, People's Republic of China.
Shengqiang
S
Chen
Translational Medicine Center, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, People's Republic of China.
Hang
H
Su
Department of Neurosurgery, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, People's Republic of China.|Institute of Neuroscience, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and Ministry of Education of China, Guangzhou Medical University, Guangzhou 510260, People's Republic of China.
Zhongmin
Z
Yuan
Department of Oncology, The First Affiliated Hospital, Jinan University, Guangzhou 510632, People's Republic of China.
Meng
M
Xu
Translational Medicine Center, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, People's Republic of China.|Department of Medical Oncology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, People's Republic of China.
Jingqi
J
Chen
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D001254:Astrocytoma / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D015415:Biomarkers; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D004195:Disease Models, Animal; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D064593:Heterografts; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D020935:MAP Kinase Signaling System; D008297:Male; D051379:Mice; D008875:Middle Aged; D060787:Neoplasm Grading; D047368:Tumor Burden; D055815:Young Adult
D015415:Biomarkers; D051860:Fragile X Messenger Ribonucleoprotein 1; D019394:Ki-67 Antigen
MEK/ERK signaling pathway; RNA interference; astrocytoma; fragile X mental retardation protein; proliferation
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