Melitoxin Inhibits Proliferation, Metastasis, and Invasion of Glioma U251 Cells by Down-regulating F2RL1.

As the principal active component of bee venom, melittin has an anti-cancer effect in different cancers. This study was aimed to investigate the effect of melittin in glioma and explore whether F2RL1 is closely involved in glioblastoma cells proliferation. TCGA and GES databases were used to evaluate the role of F2RL1 in gliomas. The U251 cells were divided into a control lentivirus + PBS group (NC-PBS), F2RL1 intervention lentivirus + PBS group (KD-PBS), control lentivirus + melittin group (NC-melittin), and F2RL1 intervention lentivirus + melittin group (KD-melittin). Cell proliferation was detected by MTT and EDU staining assays. The apoptosis rate was assessed by flow cytometry. Expressions of genes related to apoptosis, cycle arrest, migration, and invasion were detected by qRT-PCR. Cellular LDH concentrations were detected by ELISA. The subcutaneous tumor volume of nude mice was analyzed by xenograft method. F2RL1 was significantly overexpressed in glioma tissues and were reduced in the melittin-treated group compared to the blank group. F2RL1 knockdown and melittin alone or in combination increased the proportion of cells in the G1-phase, and the combination was more pronounced. The KD-melittin group showed a decrease in the number of viable cells at 24, 48, 72, and 96 h compared to the NC-PBS group. The number of cell migration and invasion was decreased in the KD-melittin group compared to the other groups. Moreover, the genes related to cell cycle arrest and apoptosis were significantly changed in the KD-melittin group. At weeks 4, 5, and 6, the tumor volume in the KD-melittin group was smaller than that in the KD-PBS group and NC-melittin group. Interference with the target gene F2RL1 inhibited the proliferation of glioma U251 cells, and melittin treatment inhibited the proliferation of glioma U251 cells. Melittin inhibited the proliferation of glioma U251 cells by suppressing the expression of target gene F2RL1.

The Value of H2BC12 for Predicting Poor Survival Outcomes in Patients With WHO Grade II and III Gliomas.

Purpose: Glioma is a common primary malignant brain tumor. Grade II (GII) gliomas are prone to develop into anaplastic grade III (GIII) gliomas, which indicate a higher malignancy and poorer survival outcome. This study aimed to satisfy the increasing demand for novel sensitive biomarkers and potential therapeutic targets in the treatment of GII and GIII gliomas. Methods: A TCGA dataset was used to investigate the expression of H2BC12 mRNA in GII and GIII gliomas and its relation to clinical pathologic characteristics. Glioma tissues were collected to verify results from the TCGA dataset, and H2BC12 mRNA was detected by RT-qPCR. ROC analysis was employed to evaluate the classification power for GII and GIII. The significance of H2BC12 mRNA GII and GIII gliomas was also investigated. In addition, H2BC12 expression-related pathways were enriched by gene set enrichment analysis (GSEA). DNA methylation level and mutation of H2BC12 were analyzed by the UALCAN and CBioPortal databases, respectively. Results: Based on the sample data from multiple databases and RT-qPCR, higher expression of H2BC12 mRNA was found in GII and GIII glioma tissue compared to normal tissue, which was consistent with a trend with our clinical specimen. H2BC12 mRNA had a better power in distinguishing between GII and GIII and yielded an AUC of 0.706 with a sensitivity of 76.9% and specificity of 81.8%. Meanwhile, high H2BC12 levels were associated with IDH status, 1p/19q codeletion, primary therapy outcome, and the histological type of gliomas. Moreover, the overall survival (OS), disease-specific survival (DSS), and progress-free interval (PFI) of GII glioma patients with higher levels of H2BC12 were shorter than those of patients with lower levels as well as GIII patients. In the multivariate analysis, a high H2BC12 level was an independent predictor for poor survival outcomes of gliomas. The Wnt or PI3K-AKT signaling pathways, DNA repair, cellular senescence, and DNA double-strand break repair were differentially activated in phenotypes that were positively associated with H2BC12. H2BC12 DNA methylation was high in TP53 nonmutant patients, and no H2BC12 mutation was observed in gliomas patients. Conclusion: H2BC12 is a promising biomarker for the diagnosis and prognosis of patients with WHO grade II and III gliomas.

Coexistence of Pituitary Adenoma and Primary Pituitary Lymphoma: A Case Report and Review of the Literature.

In the pituitary sella, the coexistence of pituitary adenoma and primary pituitary lymphoma is exceedingly rare. Thus far, only six cases have been reported. Here, we present the seventh case of coexisting pituitary adenoma and primary pituitary lymphoma, which was difficult to differentiate from other sellar tumors. To our knowledge, this is the first case of the prolactin subtype of the pituitary adenoma in literature. We have also systematically reviewed the literature and summarized the characteristics of coexisting pituitary adenoma and lymphoma. We believe this report provides a new clinical reference for the diagnosis and treatment of collision tumors of pituitary adenoma and lymphoma.

41-year-old male with a pituitary mass.

Cranial coronal T1-weighted magnetic resonance imaging with contrast enhancement showed a sellar irregular lesion (Figure A). Hematoxylin and eosin staining showed two different morphologies. The majority of tumor cells had medium-sized to large cells with a high nucleus to cytoplasm ratio, vesicular nuclei with prominent nucleoli, and poor adhesion (Figure B), which revealed positive expression of CD20 by Immunohistochemistry (Figure C). The other component showed abundant cytoplasm, spindle-like to ovoid nucleus and rare mitotic figures (Figure D). These tumor cells were positive for Pit-1 (Figure E) and perinuclear punctated structures immunopositive for CK18 (Figure F).

Adipose-derived mesenchymal stem cells-derived exosome-mediated microRNA-342-5p protects endothelial cells against atherosclerosis.

Exosomes are reported to mediate several disease-related microRNAs (miRNAs) to affect the progression of diseases, including atherosclerosis. Here, we aimed to screen the atherosclerosis-associated miRNAs and preliminarily investigate the potential regulatory mechanism of atherosclerosis. First, the lesion model for human umbilical vein endothelial cells (HUVECs) was favorably constructed. Later, through RNA-sequencing and bioinformatics analyses, miR-342-5p was identified in lesion model for HUVECs. MiR-342-5p overexpression or knockdown evidently promoted or inhibited the apoptosis of HUVECs impaired by H2O2. Mechanistically, PPP1R12B was found to have great potential as a target of miR-342-5p in HUVECs impaired by H2O2, supported by RNA-sequencing and a series of bioinformatics analyses. Meanwhile, the effect of miR-342-5p on PPP1R12B expression in HUVECs' lesion model was explored, revealing that miR-342-5p had an inhibitory role in PPP1R12B expression. Additionally, adipose-derived mesenchymal stem cells (ADSCs) in spindle-like shape and their derived exosomes with 30 to 150 nm diameter were characterized. Furthermore, results showed miR-342-5p was evidently decreased in the presence of ADSCs-derived exosomes. These findings indicated ADSCs-derived exosomes restrained the expression of miR-324-5p in lesion model. Collectively, this work demonstrates an atherosclerosis-associated miR-342-5p and reveals a preliminary possible mechanism in which miR-342-5p mediated by ADSCs-derived exosomes protects endothelial cells against atherosclerosis.

Long noncoding RNA DANCR mediates cisplatin resistance in glioma cells via activating AXL/PI3K/Akt/NF-κB signaling pathway.

Malignant glioma is an aggressive type of brain tumor with poor prognosis and mostly incurable. Although cisplatin is used for adjuvant chemotherapy against glioma, intrinsic and acquired resistance restricts the application of cisplatin. Long noncoding RNA (lncRNA) DANCR is reported to regulate the differentiation and progression of several cancers. However, whether DANCR participates in cisplatin resistance of glioma is still unknown. In this study, we found that DANCR expression was negatively correlated with cisplatin sensitivity in glioma cells. Gain-of and loss-of function assays revealed that DNACR attenuated cisplatin-induced cell proliferation inhibition in vitro and xenograft growth suppression in vivo. Furthermore, DNACR also attenuated cisplatin-induced cell apoptosis in vitro and in vivo. Mechanistically, we found that DANCR upregulated AXL via competitively binding miR-33a-5p, miR-33b-5p, miR-1-3p, miR-206, and miR-613. Through upregulating AXL, DANCR activated PI3K/Akt/NF-κB signaling pathway in glioma cells. Inhibiting AXL/PI3K/Akt/NF-κB signaling pathway reversed the effects of DANCR on cisplatin resistance. In conclusion, we identified a cisplatin-resistance associated lncRNA DANCR. DANCR promotes cisplatin resistance via activating AXL/PI3K/Akt/NF-κB signaling pathway in glioma. Our data suggested that DANCR would be a potential biomarker for predicting cisplatin sensitivity and a therapeutic target for enhancing cisplatin efficacy in glioma.

Golgi Phosphoprotein 3 Inhibits the Apoptosis of Human Glioma Cells in Part by Downregulating N-myc Downstream Regulated Gene 1.

BACKGROUND Golgi phosphoprotein 3 (GOLPH3) has been reported to be involved in the development of several human cancers. Our previous study showed that GOLPH3 expression in glioma tissues was related to the severity of the malignancy of the cancer. However, the mechanism by which GOLPH3 affects cell apoptosis is largely unknown. The present study was designed to explore the possible mechanism of GOLPH3 in cell apoptosis. MATERIAL AND METHODS To analyze the biological role of GOLPH3 in glioma cells, we used GOLPH3 small interference RNA in apoptosis of glioma cells. The apoptosis of glioma cells was detected by flow cytometry. The expression level of GOLPH3 and NDRG1 protein was determined by Western blot analyses and immunohistochemical staining, respectively, to evaluate their association with glioma. Tumor tissues were collected from patients with glioma. Normal cerebral tissues were acquired from cerebral trauma patients undergoing internal decompression surgery. RESULTS We confirm that the decrease of GOLPH3 that promotes the apoptosis of glioma cells may be regulated by the activation of NDRG1 and cleaved capcase 3. There was a inverse association between GOLPH3 and NDRG1 in glioma samples. CONCLUSIONS Our findings indicate that GOLPH3 and NDRG1 both play an important role in glioma etiology. Either GOLPH3 or NDRG1 might be a potential candidate for malignant glioma therapy.

Protein phosphatase 4 catalytic subunit is overexpressed in glioma and promotes glioma cell proliferation and invasion.

Protein phosphatase 4 catalytic subunit (PP4C) has been identified to be overexpressed in various solid cancers. However, to date, the role of PP4C in glioma remains elusive. In the present study, we aimed to detect PP4C expression in glioma patients and explore its function in glioma and prognostic significance in patients with glioma. The expression levels of PP4C mRNA and protein in 30 glioma tissue specimens and 10 non-cancerous brain tissue specimens were detected by qRT-PCR and Western blot analysis. Moreover, immunohistochemistry was performed to assess PP4C expression in 120 glioma patients. The effects of siRNA-mediated PP4C silencing on the proliferation, migration, and invasion of U251 and U87 glioma cells were assessed. We found that PP4C was upregulated in glioma tissue at both mRNA and protein levels compared with non-cancerous brain tissue. Univariate and multivariate analyses indicated that high PP4C expression was an independent prognostic factor for poor survival of glioma patients. Knockdown of PP4C reduced the proliferation, migration, and invasion of U251 and U87 cells. In conclusion, our findings suggest that PP4C plays an oncogenic role in glioma development and progression and might serve as a prognostic biomarker as well as a potential therapeutic target for glioma.