Taurine‐upregulated gene 1 (TUG1), a kind of long non‐coding RNAs (lncRNAs), was up‐regulated in ischaemic stroke (IS) with the function of promoting neuron apoptosis. In this study, we aimed to investigate the association of TUG1 polymorphisms with IS risk. The TUG1 polymorphisms were genotyped using a custom‐by‐design 48‐Plex SNPscan kit. The promoter activity was measured using the dual luciferase reporter assay. Relative expression of TUG1 in IS patients was analysed using quantitative PCR and the binding of TUG1 https://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?type=rs%26rs=rs2240183 polymorphism to transcription factor was analysed using chromatin immunoprecipitation (ChIP) assay. The https://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?type=rs%26rs=rs2240183 CT/CC genotypes and C allele in the promoter of TUG1 were associated with an increased risk of IS (CT/CC vs. TT: adjusted OR = 1.70, 95% CI, 1.16‐2.49, P = 0.006; C vs. T: adjusted OR = 1.47, 95% CI, 1.12‐1.93, P = 0.005). Logistic regression analysis showed that the https://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?type=rs%26rs=rs2240183 was a risk factor of IS besides TC, TG, HDL‐C, LDL‐C, VLDL‐C, Apo‐A1, Apo‐B and NEFA. Further functional analysis revealed that the TUG1 https://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?type=rs%26rs=rs2240183 C allele exhibited higher transcriptional activity and TUG1 expression levels (P < 0.01). The ChIP assay showed that the https://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?type=rs%26rs=rs2240183 C allele binds to transcriptional factor GATA‐1. These findings indicate that the https://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?type=rs%26rs=rs2240183 C allele was associated with a higher risk of IS possibly by binding to GATA‐1 and elevating TUG1 levels.

Background: Diosgenin, a natural steroidal saponin isolated from Trigonella foenumgraecum, has been reported to exert anti-cancer effects. Inhibitors of enhancer of zeste homology 2 (EZH2) have been widely used in treatment of cancers. However, the effects of combined treatment with diosgenin and an EZH2 inhibitor on gastric cancer (GC) cells, and the mechanism for those effects are not fully understood. Methods: AGS and SGC-7901 gastric cancer cells were treated with diosgenin (0 to 8 μM), followed by treatment with either diosgenin or an EZH2 inhibitor, GSK126 alone. Afterwards, an EZH2 overexpression plasmid and Rho inhibitor, GSK429286A was involved in cells. Cell proliferation, cell cycle distribution, and cell apoptosis, migration, and invasion were examined by CCK-8 assays, flow cytometry, and transwell assays. Western blotting was performed to detect the relative levels of protein expression. Results: Treatment with diosgenin alone caused a dose-dependent decrease in the cell viability, and combined treatment with an EZH2 inhibitor plus GSK126 caused a further significant decrease. A further analysis revealed that treatment with either diosgenin or GSK126 alone induced significant increases in G0/G1 cell cycle arrest and apoptosis, and combined treatment with both agents induced further increases in those parameters. In addition, combined treatment with diosgenin and GSK126 synergistically induced even stronger effects on impaired cell proliferation, G0/G1 phase arrest, and cell apoptosis when compared to treatment with either diosgenin or GSK126 treatment alone. At the molecular level, we demonstrated that inhibition of Rho/ROCK signaling by combined treatment with diosgenin and GSK126 could downregulate the expression of epithelial-mesenchymal transition (EMT)-related molecules. We also found that EZH2 overexpression reversed the anti-tumor effect of diosgenin by inducing cell survival, blocking G1-phase arrest, and promoted EMT. While, these biological properties were further reversed by GSK429286A. Conclusion: Collectively, combined treatment with diosgenin and GSK126 produced even more significant effects on GC cell inhibition by targeting EZH2 via Rho/ROCK signalingmediated EMT, which might be a therapeutic strategy for improving the poor therapeutic outcomes obtained with GSK126 monotherapy.

Hypoxia-inducible factor-3α (HIF-3α), a member of HIF family, can mediate adaptive responses to low oxygen and ischemia. It is believed that HIF plays crucial roles in stroke-related diseases. However, there are no reports on the association between HIF-3α genetic variants and ischemic stroke (IS) susceptibility. Therefore, we examined the association between HIF-3α gene polymorphisms (rs3826795, rs2235095, and rs3764609) and IS risk. The study population included 302 controls and 310 patients with ischemic stroke. Three polymorphisms in HIF-3α (rs3826795, rs2235095, and rs3764609) were genotyped using SNPscan technique. Our study showed a strong association of rs3826795 in HIF-3α with the risk of IS. The genotype and allele frequencies were shown to differ between the two groups. The rs3826795 in an intron of HIF-3α was related to a prominent increased IS risk (AA vs GG adjusted odd ratio [OR], 2.21; 95% confidence intervals [95% CI], 1.10–4.44; P = 0.03; AA vs AG/GG OR = 1.74, 95% CI, 1.02–2.97, P = 0.04; A vs G OR = 1.48, 95% CI, 1.05–2.07, P = 0.02). Logistic regression analysis suggested that rs3826795 posed a risk factor for IS in addition to common factors. Furthermore, when compared to controls, increased levels of homocysteic acid and level of non-esterified fatty acid were found in the cases (P < 0.01). However, no significant association was found between rs2235095 or rs3264609 and IS risk. These findings indicated that the rs3826795 polymorphism may be a potential target for predicting the risk of IS.

Introduction. A previous work has discovered that chromosome 1q32 locus linked to the risk of systemic lupus erythematosus (SLE) and miR-181b located on the susceptibility site with downregulation inversely correlating to its target molecular interferon alpha 1 (IFNA1). The purpose of this study was to investigate the association of miR-181b and IFNA1 polymorphisms with IS risk. Methods. The miR-181b rs322931, IFNA1 rs1332190, and rs10811543 were genotyped using a Multiplex SNaPshot assay. miR-181b expression levels in plasma of SLE patients and controls were analyzed using quantitative PCR. Results. The rs322931 CT, CT/TT, and T allele exerted an increased trend of SLE risk (CT vs. CC: adjusted OR=1.71, 95% CI 1.16-2.50, P=0.01; CT/TT vs. CC: adjusted OR=1.45, 95% CI 1.08-1.95, P=0.01; T vs. C: adjusted OR=1.38, 95% CI 1.07-1.79, P=0.01). Combined genotypes of the rs322931 CT/TT+rs1332190 TT and the rs322931 CC+rs10811543 AG/AA also revealed an increased risk of SLE. Gene-gene interaction analysis showed that a three-locus model consisting of rs322931, rs1332190, and rs10811543 attributed an increased risk of SLE. Further genotype-phenotype analysis revealed that rs322931 CT/TT carriers displayed lower levels of miR-181b. Conclusions. These findings indicate that the miR-181b rs322931 may be singly and jointly responsible for the etiology of SLE by altering miR-181b expression.