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In the last few years, more and more scientists have suggested and confirmed that epigenetic regulators are tightly connected and form a comprehensive network of regulatory pathways and feedback loops. This is particularly interesting for a better understanding of processes that occur in the development and progression of various diseases. Appearing on the preclinical stages of diseases, epigenetic aberrations may be prominent biomarkers. Being dynamic and reversible, epigenetic modifications could become targets for a novel option for therapy. Therefore, in this review, we are focusing on histone modifications and ncRNAs, their mutual regulation, role in cellular processes and potential clinical application. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is the most common autoimmune disease worldwide. Epigenetic alternations of microRNAs (miRNAs) can contribute to its pathogenesis and progression. As the first line therapy with DMARDs is not always successful, other drugs and therapeutic targets should be applied. This study aims to measure the expression level of plasma miRNAs in RA patients treated with olokizumab and to evaluate their potential as prognostic biomarkers. The expression of 9 miRNAs was quantified in 103 RA patients before treatment and at weeks 12 and 24 of olokizumab therapy by reverse transcription-polymerase chain reaction (RT-PCR) assay and analyzed in groups of responders and non-responders. Almost all miRNAs changed their expression during therapy. The ROC curve analysis of the most prominent of them together with consequent univariate and multivariate regression analysis revealed statistically significant associations with the olokizumab therapy efficiency scores for miR-26b, miR-29, miR-451, and miR-522. Therefore, these miRNAs might be a potential therapeutic response biomarker. [ABSTRACT FROM AUTHOR]

Abstract Renal cell carcinoma (RCC) is the second-most common uronephrological cancer. In the absence of specific symptoms, early diagnosis of RCC is challenging. Monitoring of the aberrant expression of tumour-associated antigens (TAAs) and related autoantibody response is considered as a novel approach of RCC diagnostics. The aim of this study was to examine the aberrant expression of arrestin-1 in renal tumours, to investigate the possible epigenetic mechanism underlying arrestin-1 expression, and to assess the frequency of anti-arrestin-1 autoantibody response. Immunohistochemistry was used to assess the presence of arrestin-1 in primary tumours and metastases of 39 patients with RCC and renal oncocytoma. Bisulfite sequencing was employed to analyse the methylation status of the promoter of the SAG gene encoding arrestin-1. Western blot analysis was performed to detect autoantibodies against arrestin-1 in serum samples of 36 RCC and oncocytoma patients. Arrestin-1 was found to be expressed in RCC (58.7% of cases) and renal oncocytoma (90% of cases) cells, while being absent in healthy kidney. The expression of arrestin-1 in RCC metastases was more prominent than in primary tumours. Hypomethylation of the SAG gene promoter is unlikely to be the mechanism for the aberrant expression of arrestin-1. Autoantibodies against arrestin-1 were detected in sera of 75% of RCC patients. Taken together, our findings suggest employment of autoantibody against arrestin-1 as biomarker of RCC. Highlights • Arrestin-1 is expressed in RCC tumours in 58.7% of patients. • Expression of arrestin-1 in RCC metastases is more prominent than in primary tumour. • Expression of arrestin-1 in RCC is unlikely mediated by methylation of SAG promoter. • Autoantibodies against arrestin-1 are generated in 75% of RCC patients. • Arrestin-1/autoantibodies are frequently produced in patients with renal oncocytoma. [ABSTRACT FROM AUTHOR]