ADP‐ribosylation factor 6 (ARF6) is a well‐studied protein that is involved in multiple biological functions including cell migration and invasion. The mechanism by which ARF6 regulates the migration and invasion of upper tract urothelial carcinoma (UTUC) is still unknown. MiR‐145‐5p is a tumor suppressor microRNA, which is downregulated in several cancer types. We aimed to elucidate the molecular mechanism underlying the regulation of ARF6 by miR‐145‐5p in UTUC. ARF6 expression was observed to be higher in UTUC tissues than paired adjacent normal tissues. A reverse correlation between ARF6 and miR‐145‐5p was found in UTUC tissues. MiR‐145‐5p inhibited ARF6 expression by directly targeting its 3′‐UTR. The functional studies indicated that ARF6 expression reversed the miR‐145‐5p‐reduced tumor cell migration and invasion. Notably, miR‐145‐5p reduced MMP2, N‐cadherin, FAK and MMP7, and elevated E‐cadherin protein levels in vitro; however, the above effects were reversed by ARF6. Further, the expression of epithelial‐to‐mesenchymal transition (EMT) markers and cell invasion was suppressed by knocking down MMP7 in UTUC cells. These findings suggest that miR‐145‐5p may suppress UTUC cell motility and invasion by targeting ARF6/MMP7 through EMT.
OBJECTIVE
To investigate the possible correlations among eNOS G894T polymorphism, erectile dysfunction (ED) and related risk factors in a Taiwanese population.
MATERIALS AND METHODS
In all, 151 patients with ED and 77 healthy controls were enrolled. All the men had a complete clinical history taken and laboratory data was collected. To assess erectile conditions the five‐item version of the International Index of Erectile Function (IIEF‐5) was used. The eNOS G894T polymorphisms were determined using the polymerase chain reaction‐restriction fragment length polymorphism method.
RESULTS
In all, 228 men were enrolled with a mean (sd) age of 58.6 (9.7) years. In a univariate analysis, age, serum testosterone level, and the prevalence of diabetes mellitus (DM) and hypertension were significantly different between patients with ED and the healthy controls (P < 0.01). In the multiple logistic regression analysis, DM, age and hypogonadism were three independent risk factors for ED (P = 0.018, P = 0.046 and P = 0.016, respectively). The prevalence of ED in T allele carriers (GT/TT) was significantly greater than in G allele carriers (GG; 80.0% vs 63.3%, P = 0.04). Also the eNOS 894T allele carriers had significantly lower IIEF‐5 scores than the eNOS 894G allele carriers, at 13.2 (5.3) vs 15.7 (6.1) (P = 0.01) and it was associated with increment of T allele number (11.0 (5.6) vs 13.6 (5.2) vs 15.7 (6.1); P = 0.03).
CONCLUSION
Our results indicate that DM, age and hypoganadism are three significant independent risk factors for ED. Also, in the Taiwanese population, the eNOS 894T allele carriers are at greater risk of ED, both in prevalence and severity, and this might be a factor of genetic susceptibility.
Objective: Human uncoupling proteins 2 and 3 (UCP2 and UCP3) are two mitochondrial proteins that are involved in the control of metabolism of fatty acid and possibly protect against oxidative damage. The aim of this study was to analyze genetic associations of four polymorphisms of the UCP2 and UCP3 genes with insulin, leptin concentration and obesity in Taiwan aborigines.Research methods: Four polymorphisms were compared in 324 obese (body mass index (BMI) X30 kg/m 2 ) and overweight (304BMI X25 kg/m 2 ) subjects, and 114 normal weight subjects (BMI o25 kg/m 2 ) in an aboriginal community of southern Taiwan. Anthropometric characteristics and fasting levels of insulin, leptin, triglycerides and cholesterol were measured. Results: Before and after adjusting for age distribution, only the Val55 allele in exon 4 of the UCP2 gene increased the risk of overweight and obesity (adjusted odds ratio (OR) ¼ 2.02, P ¼ 0.004) in comparison with Ala55. UCP2 V55V is also associated with higher fasting insulin levels than A55V (P ¼ 0.01) and A55A (P ¼ 0.04) in the obese/overweight group. Using the COCAPHASE program of the UNPHASED software, haplotype analysis of three single nucleotide polymorphisms (A55V-G866A-C-55T) revealed that A-G-C (73% in obese subjects and 77% in controls) was the most common haplotype and that the haplotype V-A-T (13% in obese subjects and 5% in controls) was significantly increased in obese and overweight subjects (BMI X25 kg/m 2 ) (OR ¼ 2.62, Po0.001). Discussions: UCP2 A55V variant might predispose to obesity and Val55 allele to confer population-attributable risk for 9.5% of obese disorders and increase insulin concentrations. The V-A-T haplotype within UCP2-UCP3 gene cluster is also significantly associated with obesity in Paiwan aborigines.
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