Abstract
In human cancers, miRNAs are important regulators of multiple cellular processes, and aberrant miRNA expression has been observed, and their alterations contribute to multiple cancer development and progression. Till now, little has been known about the role of miR-204 in human glioblastoma (GBM). In the present study, we used in-vitro assays to investigate the mechanisms of miR-204 in GBM cell lines and 60 cases of GBM tissues. Here, we found that miR-204 expression is downregulated in both GBM cell lines A172, U87 and U251 cells and GBM tissues as compared with NHA cells and normal tissues (all p<0.001). In addition, the ectopic expression of miR-204 suppressed A172 and U87 cell proliferation, migration and invasion. Meanwhile, miR-204 over-expression extremely inhibited the protein expression of ATF2. Notably, the enforced expression of ATF2 in A172 and U87 cells with the over-expression of miR-204 attenuated the inhibitory effects of miR-204 on proliferation, migration and invasion. In conclusion, our findings suggest that miR-204 suppressed cell proliferation, migration and invasion through inhibition of ATF2, thus, miR-204 may function as a useful drug target in the treatment and diagnosis of GBM.
Highlights
Glioblastoma multiforme (GBM) is a grade IV astrocytoma and the most lethal primary brain tumor [1]
MiR-204 function as a tumor suppressive miRNA and miR-204 expression level is down-regulated in various human malignancies: endometrial cancer [19], prostate cancer [20], medulloblastomas [21], non-small cell lung carcinoma [22, 23]
To figure out the role of miR-204 in GBM cell proliferation, we generated miR-204-overexpressing A172 and U87 cells by transiently transfecting cells with miR-204 mimics. miR-204 expression was confirmed by real time RT-PCR (Figure 2a)
Summary
Glioblastoma multiforme (GBM) is a grade IV astrocytoma and the most lethal primary brain tumor [1]. Astrocytomas are graded based on nuclear atypia, mitosis, vascular endothelial proliferation and necrosis, which define the diagnosis criteria of GBM [2]. GBM is featured with a large degree of tumor heterogeneity and easy invasion into surrounding tissues [3, 4]. The median survival time for GBM is only 14.6 months with a 2-year survival rate of 26%, they have been remarkably improved [5]. Some potential drug targets have been discovered, including transforming growth factor-β, epidermal growth factor receptor, phosphatase and tensin homolog etc, the lethality of GBM is not significantly changed due to the efforts [6, 7]. There is still much urgency for new and effective biomarkers to help find more therapeutic targeted drugs
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