RESUMEN
The human genome contains about 22 000 protein-coding genes that are transcribed to an even larger amount of messenger RNAs (mRNA). Interestingly, the results of the project ENCODE from 2012 show, that despite up to 90 % of our genome being actively transcribed, protein-coding mRNAs make up only 2-3 % of the total amount of the transcribed RNA. The rest of RNA transcripts is not translated to proteins and that is why they are referred to as "non-coding RNAs". Earlier the non-coding RNA was considered "the dark matter of genome", or "the junk", whose genes has accumulated in our DNA during the course of evolution. Today we already know that non-coding RNAs fulfil a variety of regulatory functions in our body - they intervene into epigenetic processes from chromatin remodelling to histone methylation, or into the transcription process itself, or even post-transcription processes. Long non-coding RNAs (lncRNA) are one of the classes of non-coding RNAs that have more than 200 nucleotides in length (non-coding RNAs with less than 200 nucleotides in length are called small non-coding RNAs). lncRNAs represent a widely varied and large group of molecules with diverse regulatory functions. We can identify them in all thinkable cell types or tissues, or even in an extracellular space, which includes blood, specifically plasma. Their levels change during the course of organogenesis, they are specific to different tissues and their changes also occur along with the development of different illnesses, including atherosclerosis. This review article aims to present lncRNAs problematics in general and then focuses on some of their specific representatives in relation to the process of atherosclerosis (i.e. we describe lncRNA involvement in the biology of endothelial cells, vascular smooth muscle cells or immune cells), and we further describe possible clinical potential of lncRNA, whether in diagnostics or therapy of atherosclerosis and its clinical manifestations.Key words: atherosclerosis - lincRNA - lncRNA - MALAT - MIAT.
Asunto(s)
Aterosclerosis , ARN Largo no Codificante , Aterosclerosis/fisiopatología , HumanosRESUMEN
The aim of the study was to investigate the DNA polymorphic genotype in MMP-2 promoter gene as a potential candidate region for the development of the cutaneous T-cell lymphoma (CTCL) and/or its progression. A total of 89 Czech patients with CTCL (including 23 patients with large plaque parapsoriasis) were compared to 198 controls of similar age and sex distribution, without personal or family history of chronic skin diseases and without personal history of malignancy. The three selected polymorphisms in the promoter of MMP-2 gene (-1575G/A, -1306C/T, and -790T/G) were determined using the PCR-based methodology with RFLP. In our cohort, the associated GGCCTT MMP-2 promoter genotype was highly significantly more frequent in CTCL-Ia stage patients compared to patients with parapsoriasis, the tests having high sensitivity and specificity (78%, 83%, resp.). To conclude, use of associated MMP-2 promoter genotype as a DNA marker might make it possible to distinguish between the patients with parapsoriasis and those with CTCL stage Ia, which could substantially improve possibilities of clinical diagnostics, therapy design, and prognosis of this serious condition in the early stages.
Asunto(s)
Biomarcadores de Tumor/genética , Linfoma Cutáneo de Células T/enzimología , Linfoma Cutáneo de Células T/genética , Metaloproteinasa 2 de la Matriz/genética , Regiones Promotoras Genéticas , Neoplasias Cutáneas/enzimología , Neoplasias Cutáneas/genética , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Femenino , Predisposición Genética a la Enfermedad , Humanos , Linfoma Cutáneo de Células T/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Parapsoriasis/genética , Neoplasias Cutáneas/patologíaRESUMEN
Leptin has recently attracted more attention due to its specific effects in the pathogenesis of malignancies. The aim of this study was to investigate the possible association between variants of -2548 G/A polymorphism in leptin (LEP) gene and cutaneous T-cell lymphomas (CTCL), with respect to the treatment responsiveness. A sample of 91 patients with CTCL was compared to 198 control individuals. The CTCL men with AG and/or GG genotype were more likely to receive the topical steroids treatment (odds ratio 7.88, 95% confidential interval 1.51-41.04) when compared to AA patients. Our data supports the possible involvement of LEP-2548G/A polymorphism in CTCL treatment responsiveness and thus might provide important information for individual therapy tailoring.