Gulshat Gilyazova

Prostate cancer (PrC) is one of the most common malignancies among men worldwide. However, the contribution of genetic variation in microRNA (miRNA) biogenesis pathway genes to PrC susceptibility remains poorly characterized in many ethnically diverse populations. We conducted a case–control study involving 532 PrC patients and 550 controls from the Volga-Ural region of Eurasia to evaluate the association of twenty-one single nucleotide polymorphisms (SNPs) with PrC risk using single-variant and polygenic approaches. Association analyses identified rs595055 in the AGO1 gene as significantly associated with PrC risk after correction for multiple testing. To evaluate the cumulative effect of genetic variation, weighted and unweighted polygenic risk scores (PRSs) were constructed. The weighted PRS was significantly associated with PrC risk (odds ratio per standard deviation increase = 1.63, 95% CI [1.43–1.85], P = 1.37 × 10⁻¹³), and demonstrated moderate discriminatory performance (AUC = 63.1%), outperforming the unweighted model. Individuals in the highest PRS quartile had approximately threefold higher odds of PrC than those in the lowest quartile. Combining the weighted PRS with prostate-specific antigen improved discrimination (AUC = 68.1%). These findings support the contribution of miRNA biogenesis pathway genes to PrC susceptibility and highlight the potential value of pathway-based polygenic risk stratification in understudied populations.

Abdominal fat deposition in chickens significantly impacts production efficiency and is influenced by complex genetic and molecular mechanisms. This review summarizes current genomic and transcriptomic research on the regulation of adipogenesis and fat accumulation in chickens, highlighting key genes and loci identified through genome-wide association studies as well as other candidates involved in lipogenesis, lipolysis, and transcriptional regulation. Major metabolic pathways, including MAPK, AMPK, PI3K/AKT/mTOR, TGFβ1/Smad3, FoxO, JAK–STAT, Wnt/β-catenin, and Sonic Hedgehog signaling, are examined for their roles in fat deposition. The regulatory functions of non-coding RNAs, including microRNAs, long non-coding RNAs, and circular RNAs, are discussed, focusing on their interactions with target mRNAs and signaling networks that control lipid metabolism, adipocyte differentiation, and energy balance. Integrating insights from both avian and human studies, this review emphasizes the molecular mechanisms underlying adipogenesis and highlights potential strategies for genetic selection aimed at reducing excessive abdominal fat and improving poultry productivity.

Heart failure (HF) remains a leading cause of morbidity and mortality worldwide, affecting over 30 million individuals, with its prevalence steadily increasing due to population aging. Among its forms, heart failure with preserved ejection fraction (HFpEF) has emerged as a major clinical and public health concern, now accounting for more than half of all HF cases and closely associated with comorbidities such as hypertension, obesity, and diabetes. MicroRNAs (miRNAs) have gained recognition as key regulators of the molecular mechanisms underlying HF, particularly HFpEF, where they modulate interconnected pathways of inflammation, fibrosis, and endothelial dysfunction. This review discusses the mechanisms by which miRNAs contribute to the pathogenesis of HF and examines their potential as both biomarkers and therapeutic targets. By integrating current evidence, it aims to clarify the prognostic significance and clinical applicability of these molecular markers, highlighting their role in advancing personalized strategies for the diagnosis and management of HF.

The poultry industry, a globally fast growing agricultural sector, provides affordable animal protein due to high efficiency. Gallus gallus domesticus are the most common domestic birds. Hybrid chicken breeds (crosses) are widely used to achieve high productivity. Maintaining industry competitiveness requires constant genetic selection of parent stock to improve performance traits. Genetic studies, which are essential in modern breeding programs, help identify genome variants linked to economically important traits and preserve population health. Next-generation sequencing (NGS) has identified millions of single nucleotide polymorphisms (SNPs) and insertions/deletions (INDELs), enabling detection of genome-wide regions associated with selection traits. Recent studies have pinpointed such regions using broiler lines, laying hen lines, or pooled genomic data. This review discusses advances in chicken genomic and transcriptomic research focused on traits enhancing meat breed performance and reproductive abilities. Special attention is given to transcriptome studies revealing regulatory mechanisms and key signaling pathways involved in artificial molting, as well as metagenome studies investigating resistance to infectious diseases and climate adaptation. Finally, a dedicated section highlights CRISPR/Cas genomic editing techniques for targeted genome modification in chicken genomics.

Prostate cancer (PCa) is one of the most common types of cancer among men. To date, there have been no specific markers identified for the diagnosis and prognosis or response to treatment of this disease. Thus, there is an urgent need for promising markers, which may be fulfilled by small non-coding RNAs known as microRNAs (miRNAs). Therefore, the present study aimed to investigate the miRNA profile in tissue samples obtained from patients with PCa using microarrays, followed by reverse transcriptase quantitative PCRs (RT-qPCRs). In the discovery phase, 754 miRNAs were screened in tissues obtained from patients (n = 46) with PCa in early and late stages. Expression levels of miRNA-324-3p, miRNA-429, miRNA-570, and miRNA-616 were found to be downregulated, and miRNA-423-5p expression was upregulated in patients with early-stage cancer compared to the late-stage ones. These five miRNAs were further validated in an independent cohort of samples (n = 39) collected from patients with PCa using RT-qPCR-based assays. MiRNA-324-3p, miRNA-429, miRNA-570, and miRNA-616 expression levels remained significantly downregulated in early-stage cancer tissues compared to late-stage tissues. Remarkably, for a combination of three miRNAs, PSA levels and Gleason scores were able to discriminate between patients with early-stage PCa and late-stage PCa, with an AUC of 95%, a sensitivity of 86%, and a specificity close to 94%. Thus, the data obtained in this study suggest a possible involvement of the identified miRNAs in the pathogenesis of PCa, and they may also have the potential to be developed into diagnostic and prognostic tools for PCa. However, further studies with a larger cohort are needed.

Introduction: Renal cancer ranks 10th in the mortality structure of the Russian Federation. The introduction of checkpoint inhibitors has changed the paradigm of treatment of patients with malignant neoplasms. Method: Data from clinical trials have shown good progression-free median and median overall survival. Each cancer center has been accumulating its own experience in treating patients with renal cell cancer by applying modern target drugs and immunotherapy. Result: In routine clinical practice, oncologists do not get the results that have been demonstrated in clinical trials when evaluating the effectiveness of the therapy. Conclusion: In this single-center clinical study, we discuss the results of using nivolumab as mono-therapy and the combination of nivolumab with ipilimumab in metastatic renal parenchyma cancer patients.

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.

Clear cell renal cell carcinoma (ccRCC) is characterized by high molecular genetic heterogeneity, metastatic activity and unfavorable prognosis. MicroRNAs (miRNA) are 22-nucleotide noncoding RNAs that are aberrantly expressed in cancer cells and have gained serious consideration as non-invasive cancer biomarkers. We investigated possible differential miRNA signatures that may differentiate high-grade ccRCC from primary disease stages. High-throughput miRNAs expression profiling, using TaqMan OpenArray Human MicroRNA panel, was performed in a group of 21 ccRCC patients. The obtained data was validated in 47 ccRCC patients. We identified nine dysregulated miRNAs (miRNA-210, -642, -18a, -483-5p, -455-3p, -487b, -582-3p, -199b and -200c) in tumor ccRCC tissue compared to normal renal parenchyma. Our results show that the combination of miRNA-210, miRNA-483-5p, miRNA-455 and miRNA-200c is able to distinguish low and high TNM ccRCC stages. Additionally, miRNA-18a, -210, -483-5p and -642 showed statistically significant differences between the low stage tumor ccRCC tissue and normal renal tissue. Contrariwise, the high stages of the tumor process were accompanied by alteration in the expression levels of miRNA-200c, -455-3p and -582-3p. Although the biological roles of these miRNAs in ccRCC are not totally clear, our findings need additional investigations into their involvement in the pathogenesis of ccRCC. Prospective studies with large study cohorts of ccRCC patients are important to further establish the clinical validity of our miRNA markers to predict ccRCC.

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.

Background: Renal cell carcinoma represents 3% of all adult malignancies. MicroRNAs exhibit specific functions in various biological processes through their interaction with cellular mRNA involved in apoptosis and cell cycle control. Recent studies have reported the potential association of single-nucleotide polymorphisms (SNPs) in miRNA-binding sites of VHL-HIF1α pathway genes with renal cancer development and progression. Objective: The objective of this study is to investigate the SNPs invoking an alteration in the nature of interaction with miRNA binding sites of VHL-HIF1α pathway genes. Methods: Total 450 cases of histologically and clinically verified ccRCC and 490 controls were included in our study. Genotyping was performed using a TaqMan PCR allelic discrimination method. Kaplan-Meier method of statistical analysis was implemented to analyze the overall patient survival rate. Results : Polymorphism rs10491534 in TSC1 gene was significantly associated with the risk of developing advanced ccRCC. Allele G of rs1642742 in VHL gene was significantly prevalent in ccRCC compared with the control group aged 55 and older (OR = 1.5566; CI [1.1532-2.1019]). Results from the dominant model combining individuals with AG or AA genotype showed that the A allele bearers of CDCP1 rs6773576 exhibited a higher risk of death compared to GG carriers (HR 3.93, 95% CI 1.76-17.21, log-rank P = 0.0033). Conclusion: The present study delineated the association of miRNA binding site variants in VHL- HIF1α pathway genes with the ccRCC risk, which may affect the clinical outcomes.