MiRNA-146a-A Key Player in Immunity and Diseases.

miRNA-146a, a single-stranded, non-coding RNA molecule, has emerged as a valuable diagnostic and prognostic biomarker for numerous pathological conditions. Its primary function lies in regulating inflammatory processes, haemopoiesis, allergic responses, and other key aspects of the innate immune system. Several studies have indicated that polymorphisms in miRNA-146a can influence the pathogenesis of various human diseases, including autoimmune disorders and cancer. One of the key mechanisms by which miRNA-146a exerts its effects is by controlling the expression of certain proteins involved in critical pathways. It can modulate the activity of interleukin-1 receptor-associated kinase, IRAK1, IRAK2 adaptor proteins, and tumour necrosis factor (TNF) targeting protein receptor 6, which is a regulator of the TNF signalling pathway. In addition, miRNA-146a affects gene expression through multiple signalling pathways, such as TNF, NF-κB and MEK-1/2, and JNK-1/2. Studies have been carried out to determine the effect of miRNA-146a on cancer pathogenesis, revealing its involvement in the synthesis of stem cells, which contributes to tumourigenesis. In this review, we focus on recent discoveries that highlight the significant role played by miRNA-146a in regulating various defence mechanisms and oncogenesis. The aim of this review article is to systematically examine miRNA-146a's impact on the control of signalling pathways involved in oncopathology, immune system development, and the corresponding response to therapy.

Epigenetic and Immunological Features of Bladder Cancer.

Bladder cancer (BLCA) is one of the most common types of malignant tumors of the urogenital system in adults. Globally, the incidence of BLCA is more than 500,000 new cases worldwide annually, and every year, the number of registered cases of BLCA increases noticeably. Currently, the diagnosis of BLCA is based on cystoscopy and cytological examination of urine and additional laboratory and instrumental studies. However, cystoscopy is an invasive study, and voided urine cytology has a low level of sensitivity, so there is a clear need to develop more reliable markers and test systems for detecting the disease with high sensitivity and specificity. Human body fluids (urine, serum, and plasma) are known to contain significant amounts of tumorigenic nucleic acids, circulating immune cells and proinflammatory mediators that can serve as noninvasive biomarkers, particularly useful for early cancer detection, follow-up of patients, and personalization of their treatment. The review describes the most significant advances in epigenetics of BLCA.

Exosomal MicroRNA Levels Associated with Immune Checkpoint Inhibitor Therapy in Clear Cell Renal Cell Carcinoma.

Immunotherapy with immune checkpoint inhibitors (ICIs) has shown high efficiency in clear cell renal cell carcinoma (ccRCC) treatment. However, the response to therapy among patients varies greatly. Modern studies demonstrate the high potential of exosomal miRNAs as diagnostic and prognostic markers in oncopathology. This study aimed to evaluate exosomal miRNA expression profiles of miRNAs-144, -146a, -149, -126, and -155 in patients with clear cell renal cell carcinoma treated with immune checkpoint inhibitors. The study included 35 patients whose venous blood samples were taken before and after ICI therapy. Expression analysis was performed using real-time quantitative PCR. It was demonstrated that the level of microRNA-146a increased after therapy (median(IQR) 12.92(4.06-18.90)) compared with the level before it (median(IQR) 7.15(1.90-10.50); p-value = 0.006). On the contrary, microRNA-126 was reduced after therapy with immune checkpoint inhibitors (median(IQR) 0.85(0.55-1.03) vs. 0.48(0.15-0.68) before and after therapy, respectively; p-value = 0.0001). In addition, miRNA-146a expression was shown to be reduced in patients with a higher grade of immune-related adverse events (p-value = 0.020). The AUC value for the miRNA-146a and miRNA-126 combination was 0.752 (95% CI 0.585-0.918), with the sensitivity at 64.3% and the specificity at 78.9%. Thus, while it can be assumed that miRNA-146a and miRNA-126 can be used as predictors for ICI therapy effectiveness, additional in-depth studies are required.

Exosomal miRNA-155 and miRNA-146a are promising prognostic biomarkers of the severity of hemorrhagic fever with renal syndrome.

Introduction: Hemorrhagic fever with renal syndrome (HFRS), caused by Orthohantaviruses, occupies one of the leading places among natural focal human diseases, for which there are no modern accurate and highly sensitive diagnostic methods. To improve this situation, a better understanding of the Hantavirus pathogenesis of HFRS is required. Determination of the expression level of exosomal microRNAs (miRNAs) in the serum/plasma of patients makes them potential biomarkers for diagnosing and predicting HFRS. The purpose of this study was to analyze the expression level of miRNA-146a, miRNA-126, miRNA-218, miRNA-410, miRNA-503 and miRNA-155 in patients with HFRS at different stages (fever stage, polyuric stage and convalescence stage) and with different severity of the course this disease. Materials and methods: The moderate group of patients with HFRS included 105 patients, the severe group included 99 patients, and the severe group with complications included 84 patients. Blood samples from patients with HFRS for molecular genetic analysis were collected three times: during the initial febrile period (days 1-4 of illness), the polyuric period (days 15-22 of the disease), and during convalescence. Total RNA isolation was performed using the exoRNeasy Midi Kit (Qiagen, Germany). Quantitative real-time PCR (qRT-PCR) was performed using the miRCURY LNA SYBR Green PCR Kit (Qiagen, Germany) and the LightCycler96 real-time PCR product detection system (Roche, Switzerland). Results: When comparing the expression level of exosomal miRNAs in groups of patients with different severity of the disease, a statistically significant increase in the expression level of miRNA-146a was revealed in patients with severe HFRS with complications (Fold change 2.694; p = 0.0022) compared to the group with a moderate disease form, as well as an increase in miRNA-155 expression in patients with severe and severe HFRS with complications compared to the moderate form (Fold change 1.861; p = 0.0492; Fold change 1.976; p = 0.001, respectively). Comparative analysis of the expression level of other miRNAs in patients with HFRS at various stages and with different severity of HFRS did not reveal any statistically significant results (P > 0.05). Conclusions: MiRNA-155 and miRNA-146a may be promising prognostic biomarkers in HFRS. However, further investigations are needed to evaluate the changes in the expression of miRNAs and the network of genes that can be potential targets for the studied miRNAs in order to elucidate the molecular mechanisms that can influence the occurrence and development of HFRS.