Genome-wide analyses of the prognosis-related mRNA alternative splicing landscape and novel splicing factors based on large-scale low grade glioma cohort.

Alternative splicing (AS) changes are considered to be critical in predicting treatment response. Our study aimed to investigate differential splicing patterns and to elucidate the role of splicing factor (SF) as prognostic markers of low-grade glioma (LGG). We downloaded RNA-seq data from a cohort of 516 LGG tumors in The Cancer Genome Atlas and analyzed independent prognostic factors using LASSO regression and Cox proportional regression to build a network based on the correlation between SF-related survival AS events. We collected 100 patients from our center for immunohistochemistry and analyzed survival using χ2 test and Cox and Kaplan-Meier analyses. A total of 9,616 AS events related to LGG were screened and identified as well as established related models. Through analyzing specific splicing patterns in LGG, we screened 16 genes to construct a prognostic model to stratify the risk of LGG patients. Validation revealed that the expression level of the prognostic model in LGG tissue was increased, and patients with high expression showed worse prognosis. In summary, we demonstrated the role of SFs and AS events in the progression of LGG, which may provide insights into the clinical significance and aid the future exploration of LGG-associated AS.

[Small interfering RNA-mediated α-enolase knockdown suppresses glycolysis and proliferation of human glioma U251 cells in vitro].

OBJECTIVE: To investigate the role of α-enolase (ENO1) in regulating glucose metabolism and cell growth in human glioma cells. METHODS: Glucose uptake and lactate generation were assessed to evaluate the changes in glucose metabolism in human glioma U251 cells with small interfering RNA (siRNA)-mediated ENO1 knockdown. MTT assay and 5-ethynyl-2'-deoxyuridine (EdU) staining were used to examine the cell growth and cell cycle changes following siRNA transfection of the cells. RESULTS: Transfection of U251 cells with siRNA-ENO1 markedly reduced glucose uptake (P=0.023) and lactate generation (P=0.007) in the cells and resulted in significant suppression of cell proliferation (*P<0.05) since the second day following the transfection. Transfection with siRNA-ENO1 also obviously suppressed cell cycle G1/S transition in the cells (P=0.0425). The expressions of HK2 and LDHA, the marker genes for glucose metabolism, were significantly down-regulated in the cells with siRNA-mediated ENO1 knockdown. CONCLUSION: ENO1 as a potential oncogene promotes glioma cell growth by positively modulating glucose metabolism.

Interleukin-16 polymorphism is associated with an increased risk of glioma.

OBJECTIVE: Previous studies have shown that interleukin (IL)-16 is overexpressed in human and rat gliomas. Potential links between IL-16 polymorphisms and glioma risk are currently unclear. The aim of this study was to investigate the association between IL-16 polymorphisms and glioma risk. METHODS: We examined IL-16 gene polymorphisms (i.e., rs 4778889, rs 11556218, and rs 4072111) in 216 patients with glioma and 275 controls in a Chinese population. Genotypes were determined using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Odds ratios (OR) and their corresponding 95% confidence intervals (CI) were used to evaluate the effect of the IL-16 polymorphisms on glioma risk. RESULTS: The rs 11556218TG genotype is associated with an increased risk of glioma compared with the TT genotype (OR=1.76; 95% CI, 1.22-2.54; p=0.002). Similarly, the rs 11556218G allele is associated with an increased risk of glioma compared with the T allele (OR=1.41; 95% CI, 1.06-1.87; p=0.017). However, no significant association was observed between the IL-16 rs 4778889 and rs 4072111 polymorphisms and the risk of glioma. CONCLUSION: These findings suggest that the IL-16 rs 11556218 polymorphism may be used as a susceptibility marker for glioma.

A novel functional polymorphism, 16974 A/C, in the interleukin-12-3' untranslated region is associated with risk of glioma.

Genetic factors are important in the development of glioma. Interleukin-12 (IL-12) is a multifunctional cytokine that induces Interferon (IFN)-gamma secretion and plays an important role in antitumor immunity. Interleukin-27 (IL-27) is a novel IL-12 family member, and the present studies demonstrate that IL-27 mediates a potent antitumor activity. The aim of this study was to investigate whether IL-12 and IL-27 gene polymorphisms and their serum levels are associated with glioma. We analyzed IL-12 gene 16974 A/C and IL-27 gene -964 A/G, 2905 T/G, and 4730 T/C polymorphisms in 210 patients with glioma and 220 matched controls, using polymerase chain reaction-restriction fragment length polymorphism method and DNA sequencing methods, while serum IL-12p40 and IL-27p28 levels were measured by enzyme-linked immunosorbent assay. Serum IL-12p40 and IL-27p28 levels were decreased in patients with glioma compared with controls (p < 0.01). There were significant differences in the genotype and allele frequencies of the IL-12 gene 16974 A/C polymorphism between the group of patients with glioma and the control group (p < 0.05). Moreover, genotypes carrying the IL-12 16974 C variant allele were associated with decreased serum IL-12p40 and IL-27p28 levels compared to the homozygous wild-type genotype in patients with glioma. The IL-12 gene 16974 A/C polymorphism may regulate expression of the serum IL-12p40 and IL-27p28, and associate with increased risk of glioma. Thus, genotypes carrying the IL-12 16974 C variant allele had a decreased ability to produce IL-12 and IL-27, which may contribute to glioma susceptibility.