PSMC2 is overexpressed in glioma and promotes proliferation and anti-apoptosis of glioma cells.

BACKGROUND: This study aims to investigate the effect of PSMC2 expression on the clinical prognosis of glioma patients and its molecular mechanism. METHODS: TCGA multi-tumor screening and survival analysis were combined to explore the differential expression of PSMC2 in multi-tumor. PSMC2 expression in glioma and normal tissues was detected by Western blot and RT-qPCR. Kaplan-Meier survival curve was used to visualize the effect of PSMC2 expression on the overall survival rate and disease-free survival rate of patients with glioma. The highly expressed cell line U343MG was selected to construct a PSMC2 knockdown model by siRNA transfection, and the effect of PSMC2 knockdown on cell proliferation ability was evaluated by CCK-8 assay. Gene-set enrichment analysis of PSMC2 co-expression genes was carried out to predict the molecular mechanism of their regulation of tumor cell phenotypes, and the analysis results were verified by flow cytometry and Western blot. RESULTS: Through broad-spectrum screening of 31 kinds of tumors, we found that PSMC2 was upregulated in most tumors, but PSMC2 was most significantly overexpressed in gliomas and correlated with poor prognosis in glioma patients. The results of Western blot and qRT-PCR showed that PSMC2 was significantly overexpressed in glioma tissues. Further survival analysis revealed that the overall survival and disease-free survival of patients with low PSMC2 expression were significantly better than that of patients with high PSMC2 expression. The proliferation of U343MG cells was significantly inhibited after PSMC2 knockdown. Enrichment analysis of PSMC2 co-expression genes indicated that PSMC2 affected the apoptosis process. The expression of apoptosis-related proteins also significantly changed following PSMC2 knockdown. CONCLUSIONS: PSMC2 promotes the proliferation of glioma cells and inhibits the apoptosis, which is expected to be a potential therapeutic target for glioma.

Circular RNA circ_001350 regulates glioma cell proliferation, apoptosis, and metastatic properties by acting as a miRNA sponge.

Glioma is an aggressive malignancy with increasing incidence and threatens people's health worldwide. Accumulating evidence revealed that circular RNAs (circRNAs) play important functions in cancers. A previous study demonstrated that circ_001350 was elevated in glioma tissue samples than nontumorous tissue specimens screened by high-throughput microarray. The level of circ_001350 in glioma tissue specimens and cell lines was detected by quantitative real-time polymerase chain reaction. The Fisher exact test was carried out to estimate the correlation of circ_001350 level with clinical characteristics. Cell proliferation, apoptosis, and motility abilities were detected using cell counting kit-8, clonogenic, flow cytometry, and transwell experiments, respectively. The potential target of circ_001350 was identified by the luciferase assay. circ_001350 level was significantly enhanced in glioma tissue specimens and cells. Further, elevated expression of circ_001350 was closely linked to patients' clinical severity. Knockdown of circ_001350 could inhibit cell proliferation and metastatic properties and increase apoptotic cells. circ_001350 could directly bind to miR-1236 and regulate its expression to exert oncogenic functions. Collectively, circ_001350 directly sponges miR-1236, thus contributing to malignant progression of glioma.

Upregulation of circular RNA circ_0034642 indicates unfavorable prognosis in glioma and facilitates cell proliferation and invasion via the miR-1205/BATF3 axis.

Accumulating studies demonstrate the critical role of circular RNAs (circRNAs) in the pathogenesis of various types of cancers. Previously, hsa_circ_0034642 has been found elevated in glioma tissues compared with the normal tissues, as proved by high-throughput microarray. We further investigated its expression level in 52 paired tissues and different glioma cell lines by quantitative reverse transcription-polymerase chain reaction. In addition, Fisher's exact test, Kaplan-Meier curves, and Cox analyses were performed to elucidate the clinical significance of hsa_circ_0034642. For the part of functional assays, gain/loss-of-function assays were conducted to measure cell growth, apoptosis, and metastatic properties affected by hsa_circ_0034642. Furthermore, the mechanisms of hsa_circ_0034642 were investigated by dual-luciferase reporter assays. As the results demonstrated, hsa_circ_0034642 was boosted in glioma tissues and cells. Overexpression of hsa_circ_0034642 was associated with clinical severity and poor prognosis. What is more, elevated hsa_circ_0034642 strikingly facilitated cell proliferation, migratory and invasive capacities, and decreased apoptotic cells. Mechanistically, hsa_circ_0034642 sponges miR-1205. miR-1205 regulates BATF3 level through targeting its 3'-untranslated region. In summary, hsa_circ_0034642 might play a key role in this malignancy.

Stathmin expression in glioma-derived microvascular endothelial cells: a novel therapeutic target.

The purpose of this study was to investigate stathmin expression and its mechanisms of action in GDMEC. Microvascular endothelial cells were isolated from human gliomas (n=68) and normal brain specimans (n=20), and purified by magnetic beads coated with anti-CD105 antibody. The expression of stathmin mRNA and protein were detected by RT-PCR and western blotting, respectively. Stathmin expression was silenced by application of specific siRNA in high grade GDMEC. The proliferation, apoptosis and invasion behavior of GDMEC were investigated. The stathmin positive rate of endothelial cells in normal brain, grade I-II glioma and grade III-IV glioma was 20, 66 and 95.5%, respectively (P<0.05). When cells were treated with siRNA to silence stathmin, cell viability was reduced, the apoptosis rate increased and the migration of vascular endothelial cells was suppressed significantly (P<0.05). Down-regulation of stathmin suppressed neoangiogenesis of glioma and provides a potential target for glioma treatment.