Ribonuclease A Family Member 2 Promotes the Malignant Progression of Glioma Through the PI3K/Akt Signaling Pathway.

The treatment of patients with glioma still faces many difficulties. To further optimize treatment, it is necessary to identify more accurate markers as treatment targets and predict prognostic indicators. RNASE2 was identified as a differentially expressed gene (DEG) in glioma tissues using bioinformatics analysis. In glioma microarrays, 31.21% (54/173) and 68.79% (119/173) patients showed low and high RNASE2 protein expression levels, respectively. RNASE2 protein levels were considerably correlated with age, WHO grade, relapse, and death. Both mRNA and protein levels were associated with the overall survival of patients with glioma. To investigate the role of RNASE2, it was overexpressed or silenced in glioma cells. RNASE2 overexpression promoted cell proliferation, migration, and invasion. In addition, its overexpression promoted the growth of subcutaneous tumors and lung metastasis of glioma cells. Key protein levels in the PI3K/Akt signaling pathway were upregulated by RNASE2 overexpression. In contrast, RNASE2 knockdown had the opposite effects. Furthermore, LY294002 blocked the effects of RNASE2 on the cell function of glioma cells. In conclusion, RNASE2 is a novel marker associated with the diagnosis and prognosis of patients with glioma, and it promotes the malignant progression of gliomas through the PI3K/Akt signaling pathway.

CircSKA3 Downregulates miR-1 Through Methylation in Glioblastoma to Promote Cancer Cell Proliferation.

BACKGROUND: Circular RNA circSKA3 plays an oncogenic role in breast cancer, while its role in glioblastoma (GBM) is unknown. This study aimed to explore the role of circSKA3 in GBM. METHODS: Differential expression of circSKA3 and miR-1 in GBM and adjacent non-cancer tissue samples were analyzed by RT-qPCR. GBM cells were transfected with circSKA3 expression vector or miR-1 mimic, followed by RT-qPCR to explore the potential crosstalk between them. Methylation-specific PCR (MSP) was carried out to assess the role of circSKA3 in regulating the methylation of miR-1 gene. The role of circSKA3 and miR-1 in regulating GBM cell proliferation was analyzed by CCK-8 assay. RESULTS: We found that circSKA3 was upregulated in GBM and inversely correlated with miR-1 across GBM tissues. High expression levels of circSKA3 and low expression levels of miR-1 were significantly correlated with the poor survival of GBM patients. In GBM cells, overexpression of circSKA3 increased the methylation of miR-1 gene and decreased the expression of miR-1. CCK-8 assay showed that overexpression of circSKA3 reduced the inhibitory effects of miR-1 on cell proliferation. CONCLUSION: Therefore, circSKA3 may downregulate miR-1 through methylation in GBM to promote cancer cell proliferation.

Amniotic Mesenchymal Stem Cells Decrease Aß Deposition and Improve Memory in APP/PS1 Transgenic Mice.

Transplantation of human amniotic mesenchymal stem cells (hAM-MSCs) seems to be a promising strategy for the treatment of neurodegenerative disorders, including Alzheimer's disease (AD). However, the clinical therapeutic effects of hAM-MSCs and their mechanisms of action in AD remain to be determined. Here, we used amyloid precursor protein (APP) and presenilin1 (PS1) double-transgenic mice to evaluate the effects of hAM-MSC transplantation on AD-related neuropathology and cognitive dysfunction. We found that hAM-MSC transplantation into the hippocampus dramatically reduced amyloid-ß peptide (Aß) deposition and rescued spatial learning and memory deficits in APP/PS1 mice. Interestingly, these effects were associated with increasing in Aß-degrading factors, elevations in activated microglia, and the modulation of neuroinflammation. Furthermore, enhanced hippocampal neurogenesis in the subgranular zone (SGZ) of the dentate gyrus (DG) and enhanced synaptic plasticity following hAM-MSC treatment could be another important factor in reversing the cognitive decline in APP/PS1 mice. Instead, the mechanism underlying the improved cognition apparently involves a robust increase in hippocampal synaptic density and neurogenesis that is mediated by brain-derived neurotrophic factor (BDNF). In conclusion, our data suggest that hAM-MSCs may be a new and effective therapy for the treatment of AD.

Tetra-sulfonate phthalocyanine zinc-bovine serum albumin conjugate-mediated photodynamic therapy of human glioma.

BACKGROUND: Glioma is the most common brain malignancy with poor prognosis. The current treatments for gliomas are mainly based on surgery, chemotherapy, and radiotherapy, which exhibit limited efficacy. Photodynamic therapy (PDT) using photosensitizers has been applied to glioma therapy. However, different photosensitizers usually lead to different therapeutic effects and adverse reactions. OBJECTIVE: This study investigates the anti-tumor effect of photosensitizer ZnPcS4-BSA in xenograft glioma tumors. METHODS: The xenograft glioma tumor model was established by inoculating nude mice with U251 cells. Tumor growth was evaluated by tumor volume, weight, and inhibition rate. Cell apoptosis was evaluated using TUNEL staining. Vascular endothelial growth factor (VEGF) expression and microvessel density were measured by immunohistochemistry. RESULTS: Significant decreases in tumor volume and weight as well as significant increases in tumor inhibition rate, cell apoptosis, VEGF expression, and microvessel density were observed in mice in the low- and high-dose PDT groups compared to the control, irradiation alone, and photosensitizer alone groups. No significant difference in cytotoxicity was observed between control group and photosensitizer alone group. Photosensitizer ZnPcS4-BSA significantly inhibited xenograft glioma tumor growth through induction of apoptosis. CONCLUSION: PDT using ZnPcS4-BSA may be effective for the therapy of gliomas.

Rho-associated protein kinase modulates neurite extension by regulating microtubule remodeling and vinculin distribution.

Rho-associated protein kinase is an essential regulator of cytoskeletal dynamics during the process of neurite extension. However, whether Rho kinase regulates microtubule remodeling or the distribution of adhesive proteins to mediate neurite outgrowth remains unclear. By specifically modulating Rho kinase activity with pharmacological agents, we studied the morpho-dynamics of neurite outgrowth. We found that lysophosphatidic acid, an activator of Rho kinase, inhibited neurite outgrowth, which could be reversed by Y-27632, an inhibitor of Rho kinase. Meanwhile, reorganization of microtubules was noticed during these processes, as indicated by their significant changes in the soma and growth cone. In addition, exposure to lysophosphatidic acid led to a decreased membrane distribution of vinculin, a focal adhesion protein in neurons, whereas Y-27632 recruited vinculin to the membrane. Taken together, our data suggest that Rho kinase regulates rat hippocampal neurite growth and microtubule formation via a mechanism associated with the redistribution of vinculin.