MiR-124-5p inhibits the growth of high-grade gliomas through posttranscriptional regulation of LAMB1.
BACKGROUND
Glioblastoma multiforme (GBM) is the most aggressive form of human brain tumor. It was previously shown that high levels of laminin-8 expression were a predictor of tumor recurrence and patient survival. It is thus important to elucidate the mechanism by which laminin-8 expression is regulated and determine how this contributes to glioma progression. This study investigated the mechanism of regulation of LAMB1, which encodes the β1 chain of laminin-8, in glioma cells lines and in a mouse model of GBM.


METHODS
The expression levels of LAMB1 and miR-124-5p were examined in glioma cell lines (U87 and U251) and GBM tissue samples by quantitative PCR and Western blotting. The potential regulation of LAMB1 by miR-124-5p was investigated by assessing the effects of restored miR-124-5p expression on cell proliferation, colony formation, and tumor growth and angiogenesis. The effects of inhibiting LAMB1 on tumor growth and angiogenesis were also assessed.


RESULTS
The upregulation of LAMB1 expression was highly correlated with the downregulation of miR-124-5p. LAMB1 protein expression was suppressed by miR-124-5p. The restoration of miR-124-5p expression suppressed glioma growth by inhibiting angiogenesis, effects that were also observed upon LAMB1 knockdown.


CONCLUSIONS
The findings indicate that miR-124-5p functions as a tumor suppressor and could serve as a molecular marker for glioma diagnosis and as a potential therapeutic target in GBM treatment.
Department of Neurosurgery, Institute of Neurosurgery, Key Laboratory on Brain Function Repair and Regeneration of Guangdong, Zhujiang Hospital, Southern Medical University, Guangzhou, China (Q.C., G.L., Y.C., R.X., Y.K., S.Z.); Department of Pathology, Zhujiang Hospital, Southern Medical University, Guangzhou China (Y.L.); Department of Neurosurgery, The First Affiliated Hospital of Nanchang University, Nanchang, China (G.L.).
Qiang
Q
Chen
Guohui
G
Lu
Yingqian
Y
Cai
Yufa
Y
Li
Ruxiang
R
Xu
Yiquan
Y
Ke
Shizhong
S
Zhang
D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000235:genetics*; D006801:Humans; D007797:Laminin / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D012323:RNA Processing, Post-Transcriptional
C478221:LAMB1 protein, human; D007797:Laminin; C509207:MIRN124 microRNA, human; D035683:MicroRNAs
LAMB1; glioma; laminin-8; miR-124-5p