The expression of microRNA 21 (miR-21) has been reported to be upregulated in various types of cancer, including malignant gliomas. However, its functions and mechanisms in glioma remain to be fully elucidated. The present study established miRNA-21 overexpression and knockdown cell lines using SRY-box 2 (Sox2) small interfering RNA (siRNA) to knockdown expression and Sox2 cDNA was cloned into pcDNA 3.1 mammalian expression vector for ectopic expression. BIO and XAV-939 were used for β-catenin signaling activation and knockdown, respectively. Transwell chambers were used to assay the capacity of cells to migrate. The present study determined that increased expression of miR-21 significantly promoted the migration and invasion of glioma cells, which was accompanied by an upregulated expression of the Sox2 protein. Sox2 overexpression also promoted glioma cell migration and invasion, whereas Sox2 siRNA markedly reduced the miR-21-enhanced migration and invasion of glioma cells, indicating Sox2 may act as a crucial mediator of miR-21 function. Furthermore, miR-21 also upregulated the protein expression level of β-catenin, whereas anti-miR-21 and Sox2 knockdown significantly reduced β-catenin expression. BIO, a β-catenin specific agonist, enhanced migration and invasion of glioma cells. XAV-939, an inhibitor of β-catenin signaling, markedly inhibited the migration and invasion of glioma cells, suggesting that β-catenin may be associated with miR-21- and Sox2-induced invasion of glioma cells. Notably, BIO restored the migration and invasion potential of glioma cells, which were inhibited by Sox2 siRNA and anti-miR-21. These findings indicated that β-catenin may be an important downstream mediator of miR-21 and Sox2. Therefore, the present study identified the miR-21/Sox2/β-catenin signaling pathway, which may regulate the migration and invasion of human glioma cells.

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The rupture of intracranial aneurysm (IA) is the leading cause for devastating subarachnoid hemorrhage. This study aimed to investigate genes related to IA and potential diagnosis targets. Two data sets (GSE15629 and GSE54083) were downloaded from Gene Expression Omnibus database. GSE15629 contained eight RI (ruptured IA), six UI (unruptured IA) and five control IA samples. GSE54083 included 8 RI, 5 UI and 10 superficial temporal artery samples. In total, 452 differentially expressed genes (DEGs) between RI and control, and 570 DEGs between UI and control, were identified. Protein-protein interaction networks for two kinds of DEGs related to RI and UI were constructed, respectively. Module networks were searched for DEGs related to RI or UI based on WGCNA (weighted gene coexpression network analysis). In the significant modules, FOS, CCL2, COL4A2 and CXCL5 were screened as crucial nodes with high degrees. Among them, FOS and CCL2 were enriched in immune response and COL4A2 was involved in the ECM (extracellular matrix) pathway, whereas CXCL5 was related to cytokine-cytokine receptor pathway. Taken together, FOS, CCL2, COL4A2 and CXCL5 might participate in the pathogenesis of RI or UI, and could serve as potential diagnosis targets.

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Due to its high invasiveness, glioblastoma is difficult to treat by surgery, radiotherapy, chemotherapy or any combination therapy. Syndecan binding protein (SDCBP), a widely distributed intracellular scaffold protein, has an important role in both physiological and pathological process. In the current work, we have identified target sequences for miR-135a-5p and miR-124-3p in the 3'-untranslated region of the SDCBP mRNA. Therefore, we have investigated the relationship between SDCBP, miR-135a-5p and miR-124-3p in glioblastoma multiforme cells T98G and U87 in vitro and in vivo. Dual luciferase activity assay documented that SDCBP is, in fact, the target of miR-135a-5p, miR-124-3. Western blot, qRT-PCR, proliferation, migration, and invasion assays have demonstrated that of silencing SDCBP or overexpressing miR-135a-5p/miR-124-3p significantly interferes with the malignant properties of glioblastoma cells. In vivo studies have shown that silencing SDCBP or overexpressing miR-135a-5p/miR-124-3p result in a marked decrease of tumor size and prolong life of tumor-bearing mice. A therapy combining the three treatments inhibits synergistically subcutaneous tumor growth in nude mice. In conclusion, proliferation, migration and invasion of glioblastoma can be inhibited by targeted regulation of SDCBP through upregulation of miR-135a-5p and miR-124-3p.

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Background: Myocardial ischemia/reperfusion injury (IRI) is a common perioperative complication of heart and great vessels surgery, aggravating the original myocardial damage and seriously affecting the postoperative recovery of cardiac function. The aim of this study was to reveal the functional effects and potential mechanisms of notoginsenoside R1 (NG-R1) in myocardial cells injured by hypoxia-reoxygenation (H/R). Methods: The rat cardiomyocyte line H9c2 was subjected to H/R with or without NG-R1 treatment. The levels of miR-132 and HBEGF in the cell were altered by microRNA or short-hairpin RNA transfection. Cell viability, apoptosis, lactate dehydrogenase (LDH) and malondialdehyde (MDA) were monitored. Dual luciferin was used to detect the relationship between miR-132 and HBEGF. Results: NG-R1 (20 μM) had no impact on H9c2 cells, but cell viability was significantly reduced at 80 μM. NG-R1 (20 μM) protected H9c2 cells against H/R-induced cell damage, accompanied by increased cell viability, reduced cell apoptosis, and downregulation of LDH and MDA. Furthermore, the level of miR-132 was decreased in response to H/R exposure but then increased after NG-R1 treatment. When miR-132 was overexpressed, H/R-induced cell damage could be recovered. Downregulation of miR-132 limited the protective effect of NG-R1 on H/R damage. We also found that HBEGF was a direct target of miR-132. The expression of HBEGF was increased upon H/R damage, and this increase was reversed after NG-R1 treatment. Conclusions: This study demonstrated that NG-R1 markedly protected H9c2 cells against H/R-induced damage via upregulation of miR-132 and downregulation of its target protein HBEGF.