Abstract
To study the effect of the antagomiR-27a inhibitor on glioblastoma cells. The miR- 27a expression level in specimens of human glioblastoma and normal human brain tissues excised during decompression for traumatic brain injury was assessed using qRT-PCR; The predicted target gene of miR-27a was screened out through bioinformatics databases, and the predicted gene was verified using genetic report assays; the effect of antagomiR-27a on the invasion and proliferation of glioma cells was analyzed using MTT assays and 5-ethynyl-2'-deoxyuridine (EdU) labeling. A xenograft glioblastoma model in BALB-c nude mice was established to detect the effect of antagomiR-27a on tumour growth. qRT-PCR results showed that miR-27a significantly increased in specimens from glioblastoma comparing with normal human brain tissues. Th miR-27a inhibitor significantly suppressed invasion and proliferation of glioblastoma cells. FOXO3a was verified as a new target of miR-27a by Western blotting and reporter analyzes. Tumor growth in vivo was suppressed by administration of the miR-27a inhibitor. MiR-27a may be up-regulated in human glioblastoma, and antagomiR-27a could inhibit the proliferation and invasion ability of glioblastoma cells.
Highlights
Glioblastoma (GBM) is one of the most common intracranial tumors, about 60% of caes being malignant
Our previous miRNA expression profiling study indicated that miR-27a was commonly up-regulated of antagomiR-27a was significantly inhibited compared with negative control and blank control (P0.05), indicating the cellular proliferation was inhibited after transfection with antagomiR-27a (Figure 2C)
We verified that FOXO3a is a target gene of miRNA-27a: the protein expression level of FOXO3a and the activity of its report gene were significantly inhibited after overexpression of miR-27a, while they were significantly up-regulated after inhibition of miR27a, indicating that FOXO3a is a direct target gene of miR-27a
Summary
Glioblastoma (GBM) is one of the most common intracranial tumors, about 60% of caes being malignant. MiR-27a has been found to serve as an oncogene in gastric cancer, promoting the growth of gastric cells via inhibiting the expression of prihibitin (Liu et al, 2009). It has been reported in studies of lung and breast cancers (Li et al, 2010; Wang et al, 2011) it has been nearly 10 years since miR-27 was firstly found, there are few research articels on miR-27 and its function in glioblastoma
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