lncRNA PCAT-1 interacting with FZD6 contributes to the malignancy of acute myeloid leukemia cells through activating Wnt/ß-catenin signaling pathway.

Accumulating evidence has suggested the involvement of long noncoding RNAs (lncRNAs) on the acute myeloid leukemia (AML). Therefore, this study aimed to investigate the unknown function of lncRNA Prostate cancer-associated transcript-1 (PCAT-1) in AML cells. Our data found that PCAT-1 was highly expressed in AML-M1/2 and AML-M3 patients than normal controls and its expression was significantly up-regulated in AML cell lines Kasumi-6 and HL-60. The functional experiments demonstrated that knockdown of PCAT-1 remarkably inhibited proliferation, arrested cell cycle progression and triggered apoptosis of AML cells. Mechanistically, we revealed that PCAT-1 could directly interact with FZD6 protein to regulate its stability. Overexpression of FZD6 partly abolished the effects of PCAT-1 silencing on AML cells. Our integrated experiments then suggested that PCAT-1 could activate the Wnt/ß-catenin signaling pathway in an FZD6-dependent manner. Taken together, the present study indicated that PCAT-1 interacting with FZD6 to activate Wnt/ß-catenin signaling, which may play an important role in the pathogenesis of AML.

Dimethylarginine Dimethylaminohydrolase 2 (DDAH 2) Gene Polymorphism, Asymmetric Dimethylarginine (ADMA) Concentrations, and Risk of Coronary Artery Disease: A Case-Control Study.

Asymmetric dimethylarginine (ADMA) has been shown to be an independent predictor of cardiovascular diseases. Dimethylarginine dimethylaminohydrolase 2 (DDAH 2) promotes the metabolism of ADMA and plays a key role in the regulation of acute inflammatory response. With the present study, we investigated the relationship between DDAH 2 polymorphisms and risk of coronary artery disease (CAD) and its association to plasma ADMA concentrations. We used the haplotype-tagging SNP approach to identify tag SNPs in DDAH 2. The SNPs were genotyped by PCR and sequenced in 385 CAD patients and 353 healthy controls. Plasma concentrations of ADMA were determined using enzyme-linked immunosorbent assay (ELISA). A promoter polymorphism -449C/G (rs805305) in DDAH 2 was identified. Compared with the ADMA concentrations in CC genotype (0.328 ± 0.077 µmol/l), ADMA concentrations in CG + GG genotype were significantly increased (0.517 ± 0.090 µmol/l, P < 0.001). No significant associations between the -449C/G and risk of CAD were detected in the genetic models. The results of this study suggest that Genetic -499C/G polymorphism in DDAH 2 gene may affect the plasma ADMA concentrations in patients with CAD. However, it does not indicate a novel genetic risk marker for CAD.