ABSTRACT
The present study aimed to examine how the long noncoding RNA (lncRNA) RP11543N12.1 interacted with microRNA (miR)3243p to modify microglials (MIs)induced neuroblastoma cell apoptosis, which may pose benefits to the treatment of Alzhemier's disease (AD). The cell model of AD was established by treating SHSY5Y cells with amyloid ß (Aß)2535, and MI were acquired using primary cell culture technology. The lncRNAs that were differentially expressed between SHSY5Y and control cells were screened through a microarray assay and confirmed via polymerase chain reaction. In addition, overexpression of RP11543N12.1 and miR3243p was established by transfection of SHSY5Y cells with pcDNA3.1(+)RP11543N12.1 and miR3243p mimics, respectively, while downregulation of RP11543N12.1 and miR3243p was achieved by transfection with RP11543N12.1small interfering RNA (siRNA) and miR3243p inhibitor, respectively. The interaction between RP11543N12.1 and miR3243p was confirmed with a dualluciferase reporter gene assay. The results revealed that the expression levels of total and phosphorylated tau in SHSY5Y cells were significantly elevated following Aß2535 treatment (P<0.05), and RP11543N12.1 was found to be differentially expressed between the control and Aß2535treated cells (P<0.05). Furthermore, the targeted association of RP11543N12.1 and miR3243p was predicted based on miRDB4.0 and PITA databases, and then validated via the dualluciferase reporter gene assay. SHSY5Y cells transfected with siRNA or inhibitor, and treated with Aß2535 displayed cellular survival and apoptosis that were similar to the normal levels (P<0.05). Finally, coculture of MI and SHSY5Y cells transfected with RP11543N12.1siRNA/miR3243p inhibitor significantly enhanced cell apoptosis (P<0.05). In conclusion, RP11543N12.1 targeted miR3243p to suppress proliferation and promote apoptosis in the AD cell model, suggesting that RP11543N12.1 and miR3243p may be potential biomarkers and therapeutic targets for AD.
Subject(s)
Apoptosis/genetics , Gene Expression Regulation , Inflammation/genetics , Inflammation/pathology , MicroRNAs/metabolism , Microglia/pathology , Neurons/pathology , RNA, Long Noncoding/metabolism , Alzheimer Disease/genetics , Alzheimer Disease/pathology , Base Sequence , Cell Line, Tumor , Cell Survival/genetics , Female , Gene Expression Profiling , Humans , MicroRNAs/genetics , Microglia/metabolism , Models, Biological , Neurons/metabolism , RNA, Long Noncoding/genetics , tau Proteins/metabolismABSTRACT
Clinical and experimental data have demonstrated that inflammation plays fundamental roles in the pathogenesis of ischemic stroke. Interleukin-16 (IL-16) is identified as a proinflammatory cytokine that is a key element in the ischemic cascade after cerebral ischemia. We aimed to examine the relationship between the IL-16 polymorphisms and the risk of ischemic stroke in a Chinese population. A total of 198 patients with ischemic stroke and 236 controls were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing method. We found that the rs11556218TG genotype and G allele of IL-16 were associated with significantly increased risks of ischemic stroke (TG versus TT, adjusted OR = 1.88; 95% CI, 1.15-3.07; G versus T, adjusted OR = 1.54; 95% CI, 1.05-2.27, resp.). However, there were no significant differences in the genotype and allele frequencies of IL-16 rs4778889 T/C and rs4072111 C/T polymorphisms between the two groups, even after stratification analyses by age, gender, and the presence or absence of hypertension, diabetes mellitus, hypercholesterolemia, and hypertriglyceridemia. These findings indicate that the IL-16 polymorphism may be related to the etiology of ischemic stroke in the Chinese population.
