Chen Qiang, Lu Guohui, Cai Yingqian, Li Yufa, Xu Ruxiang, Ke Yiquan, Zhang Shizhong
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.).
Neuro Oncol. 2014 May;16(5):637-51. doi: 10.1093/neuonc/not300. Epub 2014 Feb 3.
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.
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.
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.
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.
多形性胶质母细胞瘤（GBM）是人类脑肿瘤中最具侵袭性的类型。先前的研究表明，层粘连蛋白-8的高表达是肿瘤复发和患者生存的一个预测指标。因此，阐明层粘连蛋白-8表达的调控机制并确定其如何促进胶质瘤进展非常重要。本研究调查了编码层粘连蛋白-8β1链的LAMB1在胶质瘤细胞系和GBM小鼠模型中的调控机制。
通过定量PCR和蛋白质印迹法检测胶质瘤细胞系（U87和U251）和GBM组织样本中LAMB1和miR-124-5p的表达水平。通过评估恢复miR-124-5p表达对细胞增殖、集落形成以及肿瘤生长和血管生成的影响，研究miR-124-5p对LAMB1的潜在调控作用。还评估了抑制LAMB1对肿瘤生长和血管生成的影响。
LAMB1表达上调与miR-124-5p下调高度相关。miR-124-5p抑制LAMB1蛋白表达。恢复miR-124-5p表达通过抑制血管生成抑制胶质瘤生长，敲低LAMB1时也观察到了同样的效果。
这些发现表明miR-124-5p起到肿瘤抑制因子的作用，可作为胶质瘤诊断的分子标志物以及GBM治疗的潜在靶点。
