RESUMO
Obesity is a worldwide health problem with an increasing trend. This condition has a significant genetic background. H19 lncRNA has been shown to protect from dietary obesity through decreasing levels of monoallelic genes in brown fat. In the current study, we aimed to find the association between two possibly functional H19 polymorphisms, namely rs217727 and rs2839698 and obesity in Iranian population. These polymorphisms have been shown to affect risk of some obesity-related conditions in different populations. The study included 414 obese cases and 392 controls. Notably, both rs2839698 and rs217727 were associated with obesity in the allelic model as well as all supposed inheritance models. In addition, after adjustment for gender, all P values remained significant. For rs2839698, the OR (95% CI) for T allele vs. C allele was 3.29 (2.67-4.05) (P-value < 0.0001). In the co-dominant model, both TT and CT genotypes were found to confer risk of obesity compared with CC genotype (OR (95% CI)= 14.02 (8.39-23.43) and 9.45 (6.36-14.04), respectively). Similarly, combination of TT and CT genotypes had an OR (95% CI) = 10.32 (7.03-15.17) when compared with CC genotype. For rs217727, the T allele was found to exert a protective effect (OR (95% CI) = 0.6 (0.48-0.75)). Moreover, in the co-dominant model, OR (95% CI) values for TT and TC genotypes vs. CC genotype were 0.23 (0.11-0.46) and 0.65 (0.49-0.87), respectively. Taken together, H19 polymorphisms may affect risk of obesity in Iranian population. It is necessary to conduct functional studies to confirm a causal relationship between the rs217727 and rs2839698 polymorphisms and obesity.
Assuntos
Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Humanos , Irã (Geográfico)/epidemiologia , Genótipo , Obesidade/epidemiologia , Obesidade/genética , Estudos de Casos e ControlesRESUMO
HAND2 antisense RNA 1 (HAND2-AS1) is a newly recognized lncRNA encoded by a gene on 4q34.1. This lncRNA has 10 exons and is predicted to have a positive effect on expression of certain genes. HAND2-AS1 is mainly considered as a tumor suppressive lncRNA in different tissues. Moreover, HAND2-AS1 has been shown to regulate expression of several targets with possible roles in the carcinogenesis through serving as a sponge for miRNAs. This lncRNA can also influence activity of BMP, TGF-ß1, JAK/STAT and PI3K/Akt pathways. Down-regulation of HAND2-AS1 in tumor tissues has been associated with larger tumor size, higher tumor grade, higher chance of metastasis and poor clinical outcome. The present study aims at summarization of the impact of HAND2-AS1 in the carcinogenesis and its potential in cancer diagnosis or prediction of cancer prognosis.
Assuntos
MicroRNAs , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , Fosfatidilinositol 3-Quinases/metabolismo , Linhagem Celular Tumoral , MicroRNAs/genética , Carcinogênese/genética , Regulação Neoplásica da Expressão Gênica , Proliferação de Células/genética , Movimento Celular/genéticaRESUMO
Regulatory T cells (Tregs) have important functions in tumor microenvironment, particularly for induction of immune evasion. In order to find the underlying mechanism of dysregulation of Tregs in breast cancer tissues, we designed the current study to appraise expression of five Treg-related long non-coding RNAs (lncRNAs), namely FLICR (FOXP3 Regulating Long Intergenic Non-Coding RNA), NEST (IFNG-AS1), RMRP (RNA Component of Mitochondrial RNA Processing Endoribonuclease), MAFTRR (MAF Transcriptional Regulator RNA) and TH2-LCR (Th2 Cytokine Locus Control Region) in paired breast cancer and nearby noncancerous tissues. Expression levels of RMRP, TH2-LCR, MAFTRR and GATA3-AS1 were significantly higher in breast cancer samples compared with non-tumoral tissues. The calculated AUC values for GATA3-AS1, TH2-LCR, RMRP and MAFTRR were 0.66, 0.63, 0.63 and 0.60, respectively. There were significant positive associations between expression level of RMRP gene in tumor tissues and nuclear grade, tubule formation and tumor sizes. In addition, there was a significant positive association between expression levels of MAFTRR genes in tumor tissues and nuclear grade. Besides, expression levels of FLICR were different among tumors with different levels of HER2/neu receptor. Taken together, Treg-associated lncRNAs might contribute to the pathogenesis of breast cancer.
Assuntos
Neoplasias da Mama , RNA Longo não Codificante , Humanos , Feminino , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Linfócitos T Reguladores/metabolismo , Citocinas/metabolismo , Regulação Neoplásica da Expressão Gênica/genética , Microambiente TumoralRESUMO
Long non-coding RNAs (lncRNAs) have been demonstrated to in the pathophysiology of multiple sclerosis (MS). In order to appraise the role of T cell-related lncRNAs in this disorder, we assessed expressions of NEST, RMRP, TH2-LCR, MAFTRR and FLICR in MS patients and healthy individuals. We detected significant difference in the expression of RMRP and FLICR between cases and controls. There were substantial correlations between expressions of NEST, RMRP, TH2-LCR, MAFTRR and FLICR lncRNAs among patients, but not controls. The strongest correlations were found between RMRP and TH2-LCR, and between MAFTRR and RMRP with correlation coefficients of 0.69 and 0.59, respectively. ROC curve analysis revealed appropriate power of FLICR in differentiating between MS patients and healthy controls (AUC value = 0.84). Expression of NEST lncRNA was positively correlated with disease duration in MS patients, but negatively correlated with age at onset. In brief, we reported dysregulation of two T cell-related lncRNAs in MS patients and proposed FLICR as a putative marker for this disorder.