Circular RNA circBFAR promotes glioblastoma progression by regulating a miR-548b/FoxM1 axis.

Glioblastoma multiforme (GBM) is the most common and aggressive type of tumor of the primary nervous system. Treatment options for GBM include surgery, chemotherapy, and radiation therapy; however, the clinical outcomes are poor, with a high rate of recurrence. An increasing number of studies have shown that circular RNAs (circRNAs) serve important roles in several types of cancer. Gene Expression Omnibus (GEO) database was utilized to identify the differentially expressed circRNAs and their biological functions. Then, we detected the circular RNA bifunctional apoptosis regulator (circBFAR) was significantly increased in three GEO datasets. However, the role of circBFAR has not been reported in GBM. In this study, the expression of circBFAR was significantly increased both in GBM tissues or cell lines and was negatively correlated with overall survival in patients with GBM. Knockdown of circBFAR inhibited proliferation and invasion both in vitro and in vivo. Increased expression of circBFAR resulted in a reduction of miR-548b expression in glioma cells. A luciferase reporter and RIP assay indicated that miR-548b was a direct target of circBFAR, and miR-548b may negatively regulate the expression of FoxM1. Rescue experiments showed that overexpression of FoxM1 could counter the effect of circBFAR silencing on the proliferation and invasion of glioma cell lines. Moreover, we identified that circBFAR regulates FoxM1 by interacting with miR-548b in glioma cells. In conclusion, the present study demonstrated that a circBFAR/miR-548b/FoxM1 axis regulates the development of GBM and highlights potentially novel therapeutic targets for the treatment of GBM.

Allicin induces apoptosis through activation of both intrinsic and extrinsic pathways in glioma cells.

Allicin is an extract purified from Allium sativum (garlic), and previous research has indicated that Allicin has an inhibitory effect on many kinds of tumor cells. The aim of the present study was to explore the anticancer activity of Allicin on human glioma cells and investigate the underlying mechanism. MTT and colony-formation assays were performed to detect glioma cell proliferation, and explore the effect of Allicin at various doses and time-points. The apoptosis of glioma cells was measured by fluorescence microscopy with Hoechst 33258 staining, and then flow cytometry was used to analyzed changes in glioma cell apoptosis. Reverse transcription­quantitative polymerase chain reaction and western blot analysis were used to detect the effect of Allicin on the expression levels of Fas/Fas ligand (FasL), caspase­3, B­cell lymphoma 2 and Bcl­2­associated X protein. Allicin suppressed the proliferation and colony formation ability of U251 cells in a dose­ and time­dependent manner. A cytotoxic effect of Allicin was observed in glioma cells in a dose­dependent manner. Changes in nuclear morphology were observed in U251 cells with Hoechst 33258 staining. The activity of caspases were significantly elevated and Fas/FasL expression levels were increased following treatment with Allicin, at both the mRNA and protein level. These results demonstrated that Allicin suppresses proliferation and induces glioma cell apoptosis in vitro. Both intrinsic mitochondrial and extrinsic Fas/FasL­mediated pathways react in glioma cell after treating with Allicin, which then activate major apoptotic cascades. These results implicate Allicin as a novel antitumor agent in treating glioma.

Astragaloside IV protects against apoptosis in human degenerative chondrocytes through autophagy activation.

Increased cell apoptosis in chondrocytes is a feature of degenerative cartilage. Astragaloside IV (AST) has been proven to possess an antiarthritic effect by preventing interleukin (IL)­1ß­induced cartilage damage. However, the role of AST on chondrocyte apoptosis and its underlying mechanism remains unknown. In the present study, degenerative chondrocytes isolated from patients with osteoarthritis (OA) were subjected to AST and IL­1ß treatment. Results indicated that AST protected against chondrocyte apoptosis induced by IL­1ß. Western blotting indicated that AST increased the protein expression of LC3­II/I and decreased P62/SQSTM1 expression, which suggested that AST upregulated autophagy activity in chondrocytes. Fluorescent protein GFP­LC3 analysis and transmission electron microscopy observation confirmed that autophagy was promoted by AST. In contrast, after autophagy inhibited by 3­methyladenine, chondrocyte apoptosis was further increased under IL­1ß treatment. Ultimately, rapamycin was used as a positive control, whose results confirmed that rapamycin­mediated autophagy also decreased chondrocyte apoptosis induced by IL­1ß. In conclusion, these results suggested that AST­mediated autophagy serves an anti­apoptotic role in chondrocytes, which may aid the development of novel therapeutic approaches for OA treatment.