MicroRNAs can coordinately repress multiple target genes and interfere with the biological functions of the cell, such as proliferation and apoptosis. In the present study, we report that miR-200b was downregulated in malignant glioma cell lines and specimens. Overexpression of miR-200b suppressed the proliferation and colony formation of glioma cells. An oncogene encoding cAMP responsive element-binding protein 1 (CREB1), which has been shown to be an important transcription factor involved in the proliferation, survival, and metastasis of tumor cells, was here confirmed as a direct target gene of miR-200b. CREB1 was also found to be present at a high level in human glioma tissues. This was inversely correlated with miR-200b expression. Ectopic expression of CREB1 attenuated the growth suppressive phenotypes of glioma cells caused by miR-200b. These results indicate that miR-200b targets the CREB1 gene and suppresses glioma cell growth, suggesting that miR-200b shows tumor-suppressive activity in human malignant glioma.

BackgroundGlioma is one of the most common malignancies of the central nervous system in adults. The lncRNA PTEN pseudogene-1 (PTENP1) has been reported to play an important role in the development and progression of various cancers. However, the molecular mechanism by which lncRNA PTENP1 affects the development and progression of gliomas remains unclear.Materials and methodsThe levels of PTENP1 expression in glioma tissues and normal brain tissues were detected by quantitative real-time PCR. Cell Counting Kit-8 and 5-ethynyl-2′-deoxyuridine staining assays were performed to detect cell proliferation. Flow cytometry was used to analyze cell cycle progression. Transwell assay and scratch test were used to detect cell migration and invasion, and Western blot studies were performed to detect protein expression.ResultsOur results showed that expression of lncRNA PTENP1 was decreased in glioma tissues when compared with normal brain tissues. Overexpression of PTENP1 suppressed SHG44 and U251 cell proliferation and significantly decreased the numbers of S-phase cells. Furthermore, the invasion and migration abilities of SHG44 and U251 cells were reduced after being transfected with a PTENP1 overexpression plasmid. Overexpression of PTENP1 induced the expression of p21 protein and suppressed the p38 signaling pathway.ConclusionOur study investigated the function of PTENP1 in glioma and provided new insights for treating that malignancy.

Lactate dehydrogenase A (LDHA) is involved in various cancers. In this study, we investigated the expression and function of LDHA in glioma. We found that LDHA was up-regulated in glioma samples. Furthermore, we found that overexpression of LDHA promoted proliferation, invasion and glycolysis in glioma cells. Luciferase reporter assays confirmed that LDHA was a direct target of miR-200b. miR-200b was found to be down-regulated in glioma samples, which was inversely correlated with LDHA expression. Repression of LDHA by miR-200b suppressed the glycolysis, cell proliferation and invasion of glioma cells. These results provide evidence that miR-200b acts as a tumor suppressor in glioma through the inhibition of LDHA both in vitro and in vivo. Targeting LDHA through miR-200b could be a potential therapeutic strategy in glioma.

Glioma is characterized by high invasion, migration and proliferation abilities. However, the molecular mechanism that triggers the development and recurrence of this tumor is also elusive. This study aims to investigate the biological function and molecular mechanism of microRNA218 in glioma. Human glioma samples were obtained and employed to investigate the correlation between microRNA218 and glioma pathological grading. Glioma cell viability was detected by the cell-counting kit-8 (CCK-8) cell counting assay. Transwell assay and wound-healing assay were employed to examine the migration and invasion of the glioma cells. The mRNA transcription and protein expression of glioma-associated oncogene homolog 1 (GLI1) were analyzed by quantitative RT-PCR and Western blot analysis, respectively. Southwestern blot assay was utilized to explore the possible interaction site of GLI1 and microRNA218. The results indicated that microRNA218 is significantly down-regulated in glioma samples and negatively correlated with the pathological grading. The cell viability was significantly decreased, and migration and invasion were significantly inhibited in microRNA218 treated cells, compared with un-treated cells. GLI1 was discovered acting as a functional downstream target of microRNA218, by which microRNA218 inhibited glioma cell migration and invasion. Southwestern blot result showed that microRNA218 targeted directly the N terminus of GLI1 molecular, and repressed the GLI1 expression in U87MG cells. In conclusion, microRNA218 could reduce the invasion and migration, and inhibit proliferation of glioma cells by suppressing the expression of GLI1 protein at the interacting with the N terminus.

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