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Glioblastoma multiforme (GBM) represents the deadliest form of brain tumour, characterized by its low survival rate and grim prognosis. Cytokines released from glioma‐associated microglia/macrophages are involved in establishing the tumour microenvironment, thereby crucially promoting GBM progression. MS4A6A polymorphism was confirmed to be associated with neurodegenerative and polymorphism disease pathobiology, but whether it participates in the regulation of GBM and the underlying mechanisms is still not elucidated. Here, we found that MS4A6A was significantly upregulated in GBM patient samples. The results from the single‐cell RNA‐sequencing (scRNA‐seq) database and immunostaining demonstrated the specific expression of MS4A6A in microglial cells. In vitro, microglial overexpression of MS4A6A stimulated the proliferation and migration of glioblastoma cells. Moreover, high MS4A6A mRNA expression was related to poor prognosis in GBM patients. Our study highlights the potential of MS4A6A as a promising biomarker for GBM, which may provide novel strategies for its prevention, diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Objective: We aimed to investigate the roles and underlying mechanisms of YAP in the proliferation of neuroblastoma cells. Methods: The expression level of YAP was evaluated by Western blotting and immunocytochemistry. Cell viability, cell proliferation and growth were detected by CCK‐8, PH3 and Ki67 immunostaining, and the real‐time cell analyser system. The nuclear and cytoplasmic proteins of p27Kip1 were dissociated by the nuclear‐cytosol extraction kit and were detected by Western blotting and immunocytochemistry. mRNA levels of Akt, CDK5 and CRM1 were determined by qRT‐PCR. Results: YAP was enriched in SH‐SY5Y cells (a human neuroblastoma cell line). Knock‐down of YAP in SH‐SY5Y cells or SK‐N‐SH cell line (another human neuroblastoma cell line) significantly decreased cell viability, inhibited cell proliferation and growth. Mechanistically, knock‐down of YAP increased the nuclear location of p27Kip1, whereas serum‐induced YAP activation decreased the nuclear location of p27Kip1 and was required for cell proliferation. Meanwhile, overexpression of YAP in these serum‐starved SH‐SY5Y cells decreased the nuclear location of p27Kip1, promoted cell proliferation and overexpression of p27Kip1 in YAP‐activated cells inhibited cell proliferation. Furthermore, knock‐down of YAP reduced Akt mRNA and protein levels. Overexpression of Akt in YAP‐downregulated cells decreased the nuclear location of p27Kip1 and accelerated the proliferation of SH‐SY5Y cells. Conclusions: Our studies suggest that YAP promotes the proliferation of neuroblastoma cells through negatively controlling the nuclear location of p27Kip1 mediated by Akt. [ABSTRACT FROM AUTHOR]

[Display omitted] Glioblastoma (GBM) is the most common malignant glioma among brain tumors with low survival rate and high recurrence rate. Columbianadin (CBN) has pharmacological properties such as anti-inflammatory, analgesic, thrombogenesis-inhibiting and anti-tumor effects. However, it remains unknown that the effect of CBN on GBM cells and its underlying molecular mechanisms. In the present study, we found that CBN inhibited the growth and proliferation of GBM cells in a dose-dependent manner. Subsequently, we found that CBN arrested the cell cycle in G0/G1 phase and induced the apoptosis of GBM cells. In addition, CBN also inhibited the migration and invasion of GBM cells. Mechanistically, we chose network pharmacology approach by screening intersecting genes through targets of CBN in anti-GBM, performing PPI network construction followed by GO analysis and KEGG analysis to screen potential candidate signaling pathway, and found that phosphatidylinositol 3-kinase/Protein Kinase-B (PI3K/Akt) signaling pathway was a potential target signaling pathway of CBN in anti-GBM. As expected, CBN treatment indeed inhibited the PI3K/Akt signaling pathway in GBM cells. Furthermore, YS-49, an agonist of PI3K/Akt signaling, partially restored the anti-GBM effect of CBN. Finally, we found that CBN inhibited GBM growth in an orthotopic mouse model of GBM through inhibiting PI3K/Akt signaling pathway. Together, these results suggest that CBN has an anti-GBM effect by suppressing PI3K/Akt signaling pathway, and is a promising drug for treating GBM effectively. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is one of the most common intracranial primary malignancies with the highest mortality rate, and there is a lack of effective treatments. In this study, we examined the anti-GBM activity of Tenacissoside H (TH), an active component isolated from the traditional Chinese medicine Marsdenia tenacissima (Roxb.) Wight & Arn (MT), and investigated the potential mechanism. Firstly, we found that TH decreased the viability of GBM cells by inducing cell cycle arrest and apoptosis, and inhibited the migration of GBM cells. Furthermore, combined with the Gene Expression Omnibus database (GEO) and network pharmacology as well as molecular docking, TH was shown to inhibit GBM progression by directly regulating the PI3K/Akt/mTOR pathway, which was further validated in vitro. In addition, the selective PI3K agonist 740 y-p partially restored the inhibitory effects of TH on GBM cells. Finally, TH inhibited GBM progression in an orthotopic transplantation model by inactivating the PI3K/Akt/mTOR pathway in vivo. Conclusively, our results suggest that TH represses GBM progression by inhibiting the PI3K/Akt/mTOR signaling pathway in vitro and in vivo , and provides new insight for the treatment of GBM patients. [Display omitted] • Combining GEO and network pharmacology to elucidate the mechanism of TH on GBM. • TH inhibits GBM progression by inhibiting PI3K/Akt/mTOR pathway in vitro and in vivo. • Orthotopic GBM model proves that TH penetrates blood-brain barrier to inhibit GBM. • Our study demonstrats the safety of TH administered in vivo. [ABSTRACT FROM AUTHOR]

Background: Abnormal expression of circular RNA (circRNA) has been shown to play an important role in the progression of cancer. However, the role of circRNAs on nonsmall cell lung cancer (NSCLC) remains largely unknown. This study aims to reveal the effects and potential mechanisms of circRNA on NSCLC cell proliferation and apoptosis. Materials and Methods: Real-time quantitative polymerase chain reaction was used to detect the expression of circ_0014130 in NSCLC tissues and cells. After silencing circ_0014130 in NSCLC cells H1299 and A549, MTT assay or flow cytometry was performed to analyze the proliferation or the apoptosis of cells, respectively. The relationships between circ_0014130, miR-142-5p, and insulin-like growth factor (IGF)-1 were validated by dual-luciferase reporter system and RNA pull-down. Western blot was used to detect the protein level of IGF-1 after the interference with circ_0014130 in NSCLC cells. Results: Circ_0014130 was abnormally highly expressed in NSCLC tissues and cells. After shRNA interfering circ_0014130 of NSCLC cells H1299 and A549, the NSCLC cell proliferation was inhibited and the cell apoptosis was promoted. By dual-luciferase reporter system and RNA pull-down assays, circ_0014130, miR-142-5p, and IGF-1 were confirmed to interact directly. After the transfection with si-circ_0014130 in NSCLC cells, the protein level of IGF-1 was reduced, and the cell proliferation was inhibited and the cell apoptosis was promoted, whereas these effects were reversed after cotransfection with miR-142-5p inhibitor. Conclusion: Our results indicated that the silencing circ_0014130 inhibited NSCLC cell proliferation and promoted cell apoptosis by upregulating miR-142-5p and downregulating IGF-1 expression. This might provide new strategies for future diagnosis and treatment of NSCLC. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is a human malignant tumor with low survival and high recurrence rate. Angelicin, an active furanocoumarin compound, has been reported to possess potential antitumor activity towards various malignancies. However, the effect of angelicin on GBM cells and its mechanism are still unclear. In this study, we found that angelicin inhibited the proliferation of GBM by inducing the cell cycle arrested in G1 phase and suppressed the migration of GBM cells in vitro. Mechanically, we found that angelicin downregulated the expression of YAP and decreased the nuclear localization of YAP, and suppressed the expression of β-catenin. Furthermore, overexpression of YAP partially restored the inhibitory effect of angelicin on GBM cells in vitro. Finally, we found that angelicin could inhibit the growth of tumor and reduce the expression of YAP in the subcutaneous xenograft model of GBM in nude mice and the syngeneic intracranial orthotopic model of GBM in C57BL/6 mice. Taken together, our results suggest that the natural product angelicin exerts its anticancer effects on GBM via YAP signaling pathway, and is expected to be a promising compound for the treatment of GBM. • Angelicin inhibits the proliferation and migration of GBM cells in vitro. • Angelicin decreases the expression and nucleus translocation of YAP in vitro. • YAP overexpression partly abolishes the inhibitory effect of angelicin in vitro. • Angelicin inhibits the growth of GBM and reduces the YAP expression in vivo. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is the most prevalent type of adult primary brain tumor and chemotherapy of GBM was limited by drug-resistance. Fraxinellone is a tetrahydro-benzofuranone derivative with various pharmacological activities. However, the pharmacological effects of fraxinellone on GBM remains largely unknown. Here, we found that fraxinellone inhibited the proliferation and growth of GBM cells in a dose-dependent manner in vitro. Subsequently, we found that fraxinellone suppressed the migration and induced apoptosis of GBM cells in vitro. Using western blot and immunostaining, we further found that fraxinellone downregulated the expressions of sirtuin 3 (SIRT3), and superoxide dismutase 2 (SOD2), a downstream of SIRT3 in GBM cells. Meanwhile, reactive oxygen species (ROS) were increased in these fraxinellone-treated GBM cells. Interestingly, overexpression of SIRT3 (SIRT3-OE) indeed partially restored the inhibition of both cell proliferation and migration of GBM cells induced by fraxinellone. Finally, we found that fraxinellone could inhibit the growth of GBM in xenograft model through the inactivation of SIRT3 signaling pathway. Taken together, these results suggest that fraxinellone suppressed the growth and migration of GBM cells by downregulating SIRT3 signaling in vitro , and inhibited the tumorigenesis of GBMs in vivo. [Display omitted] • Fraxinellone inhibited the proliferation and migration of Glioblastoma cells in vitro. • Fraxinellone triggered cell senescence and death in Glioblastoma cells. • Fraxinellone treatment decreased the expression of SIRT3 in Glioblastoma cells. • Overexpression of SIRT3 can partially restore the inhibition of cell proliferation and migration of Glioblastoma cell by fraxinellone treatment. • Fraxinellone inhibited tumor growth in vivo. [ABSTRACT FROM AUTHOR]