Role of long noncoding RNA MEG3/miR-378/GRB2 axis in neuronal autophagy and neurological functional impairment in ischemic stroke.

Autophagy has been shown to maintain neural system homeostasis during stroke. However, the molecular mechanisms underlying neuronal autophagy in ischemic stroke remain poorly understood. This study aims to investigate the regulatory mechanisms of the pathway consisting of MEG3 (maternally expressed gene 3), microRNA-378 (miR-378), and GRB2 (growth factor receptor-bound protein 2) in neuronal autophagy and neurological functional impairment in ischemic stroke. A mouse model of the middle cerebral artery occluded-induced ischemic stroke and an in vitro model of oxygen-glucose deprivation-induced neuronal injury were developed. To understand the role of the MEG3/miR-378/GRB2 axis in the neuronal regulation, the expression of proteins associated with autophagy in neurons was measured by Western blotting analysis, and neuron death was evaluated using a lactate dehydrogenase leakage rate test. First, it was found that the GRB2 gene, up-regulated in middle cerebral artery occluded-operated mice and oxygen-glucose deprivation-exposed neurons, was a target gene of miR-378. Next, miR-378 inhibited neuronal loss and neurological functional impairment in mice, as well as neuronal autophagy and neuronal death by silencing of GRB2. Confirmatory in vitro experiments showed that MEG3 could specifically bind to miR-378 and subsequently up-regulate the expression of GRB2, which in turn suppressed the activation of Akt/mTOR pathway. Taken together, these findings suggested that miR-378 might protect against neuronal autophagy and neurological functional impairment and proposed that a MEG3/miR-378/GRB2 regulatory axis contributed to better understanding of the pathophysiology of ischemic stroke.

Impact of genotype on endocrinal complications of Children with Alpha-thalassemia in China.

Alpha-thalassemia occurs with high frenquency in China. Four common α-globin gene deletion mutations (-SEA, -α3.7, and -α4.2, Haemoglobin Constant Spring (CS) mutation) were identified in Chinese patients. Individuals with alpha-thalassemia syndrome are more often of children. However report on endocrinal complications in children with alpha thalassemia in China are still absent. The present study aimed to investigate the impact of genotype on endocrinal complications in Chinese children. Association analysis between genotype and endocrinal compliaction development was conducted on 200 patients with 200 healthy controls. Hypogonadism was found to be the most prominent endocrinal complications (84.0%) leading to the growth retardation, hypogonadism, diabetes mellitus, hypothyroidism and hypoparathyroidism whose incidence were significantly higher in pateints. (αCSα/-SEA) was the main genotype of Alpha thalassemia identified in the patients (37.5%), and patients with the (-α4.2/-SEA) genotype had a higher prevalence of hypogonadism, diabetes mellitus and hypoparathyroidism (P = 0.001, P = 0.001, P < 0.001, respectively).

Association of miR-146a, miR-149, miR-196a2, miR-499 gene polymorphisms with ischemic stroke in a Chinese people.

This study aimed to investigate genetic polymorphisms of miR-146a, miR-149, miR-196a2, and miR-499 and genetic susceptibility of ischemic stroke in the population of Guangxi in China. A case-control study was used to investigate miRNAs genetic polymorphisms in 298 patients with ischemic stroke and 303 healthy controls. Single-base extension polymerase chain reaction genotyping principle was used to detect genetic polymorphisms of miRNAs,and the relationship of genotype in each group and blood lipid was compared and analyzed. The genetic polymorphism of miR-499A>G (rs3746444) was associated with ischemic stroke (P < 0.05), and the risk of ischemic stroke was high in patients with G allele (OR = 1.455; 95% CI = 0.531-2.381; P = 0.039) and AG (OR = 1.339; 95% CI = 1.126-1.967; P = 0.037) genotype. The levels of low-density lipoprotein cholesterol, very-low-density lipoprotein cholesterol, homocysteine, and lipoprotein in the ischemic stroke group were higher than those in the control group (P < 0.05). The genetic polymorphism of miR-499A>G (rs3746444) was related to ischemic stroke, and G allele and AG genotype may increase the risk of ischemic stroke in the population of Guangxi in China.

[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.