The Role of Methylation of a Group of microRNA Genes in the Pathogenesis of Metastatic Renal Cell Carcinoma.

The role of methylation of 9 miRNA genes in the pathogenesis of metastatic clear cell renal cell carcinoma was determined by quantitative methylation-specific PCR (MS-PCR). For 5 genes (MIR125B-1, MIR137, MIR193A, MIR34B/C, and MIR375), a significant correlation of high methylation level with late (III-IV) stages, large size (T3+T4) of the tumor, and metastasis to lymph nodes and/or distant organs was revealed. For another group of genes (MIR125B-1, MIR1258, MIR193A, MIR34B/C, and MIR375), a statistically significant correlation of high methylation level with loss of differentiation in the tumor (G3-G4) was found, and the opposite pattern was found for MIR203A.

Acceleration of CRISPR/Cas9-Mediated Editing at Multiple Sites in the Genome.

The application of the CRISPR/Cas9-based genome editing technique to the yeast has made it possible to simultaneously modify several sites, particularly to integrate several expression cassettes. The existing methods provide high efficiency for such modifications; however, common protocols include several preparatory steps, namely, the construction of an intermediate Cas9-expressing strain, the assembly of a plasmid bearing several single guide RNA (sgRNA) expression cassettes, and the surrounding integrated DNA fragments with long flanks for recombination with target loci. Since these preparatory steps are time consuming and may not be desirable in some types of experiments, we explored the possibility of multiple integration without these steps.

Long Non-Coding RNAs and microRNAs Groups in the Regulation of Expression Level of a Number of Tumor-Associated Genes in Ovarian Cancer.

The search for interacting long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and mRNAs of protein-coding genes through the mechanism of competing endogenous RNAs in tumors of ovarian cancer patients was carried out. The levels of expression of 24 lncRNAs, 20 miRNAs, and 28 mRNAs of protein-coding genes involved in oncogenesis were determined by real-time PCR on a set of representative samples. Correlations between lncRNAs/miRNA and miRNA/mRNA levels in ovarian cancer samples were analyzed.

The Correlation of Ten Immune Checkpoint Gene Expressions and Their Association with Gastric Cancer Development.

In the immunotherapy based on immune checkpoint inhibition (IC), additional ICs are being studied to increase its effectiveness. An almost unstudied feature is the possible co-expression of ICs, which can determine the therapeutic efficacy of their inhibition. For the selection of promising ICs, information on the association of their expression with cancer development may be essential.

The Features of Checkpoint Receptor-Ligand Interaction in Cancer and the Therapeutic Effectiveness of Their Inhibition.

To date, certain problems have been identified in cancer immunotherapy using the inhibition of immune checkpoints (ICs). Despite the excellent effect of cancer therapy in some cases when blocking the PD-L1 (programmed death-ligand 1) ligand and the immune cell receptors PD-1 (programmed cell death protein 1) and CTLA4 (cytotoxic T-lymphocyte-associated protein 4) with antibodies, the proportion of patients responding to such therapy is still far from desirable. This situation has stimulated the exploration of additional receptors and ligands as targets for immunotherapy.

The Features of Immune Checkpoint Gene Regulation by microRNA in Cancer.

Currently, the search for new promising tools of immunotherapy continues. In this regard, microRNAs (miRNAs) that influence immune checkpoint (IC) gene expression in tumor and T-cells and may be important regulators of immune cells are considered. MiRNAs regulate gene expression by blocking mRNA translation.

Tree-ring data set for dendroclimatic reconstructions and dendrochronological dating in European Russia.

The data set presented represents 15 years of collection. It contains tree-ring width measurements from 64 sites of living trees and ten historical chronologies based on archaeological and construction wood up to year 572 CE, altogether 2909 tree-ring series and more than 450000 measured and cross-dated tree rings. It covers the vast territory of European Russia, including its forested northern and central parts, and the Northern Caucasus mountains.

Panel of Candidate Genes to Predict the Survival of Patients with Clear Cell Renal Cancer on the Basis of Gene Expression Regulated by HIF1α/HIF2α.

The detection of genes related to the lifetime of patients with clear cell renal cancer provides information on the mechanisms of the tumor development and can be the basis for creating approaches to predict patient survival. In this paper, the expression of genes regulated by the HIF2α transcriptional factor was studied. Based on the results obtained here and previously identified genes regulated by the transcriptional factor HIF1α, a new panel of 6 genes, including the BAP1 gene, was proposed.

Aberrant Methylation of 20 miRNA Genes Specifically Involved in Various Steps of Ovarian Carcinoma Spread: From Primary Tumors to Peritoneal Macroscopic Metastases.

Our work aimed to differentiate 20 aberrantly methylated miRNA genes that participate at different stages of development and metastasis of ovarian carcinoma (OvCa) using methylation-specific qPCR in a representative set of clinical samples: 102 primary tumors without and with metastases (to lymph nodes, peritoneum, or distant organs) and 30 peritoneal macroscopic metastases (PMM). Thirteen miRNA genes (, , , , , , , , , , , , and ) were hypermethylated already at the early stages of OvCa, while hypermethylation of , , , and was pronounced in metastatic tumors, and showed high methylation levels specifically in PMM. We confirmed the significant relationship between methylation and expression levels for 11 out of 12 miRNAs analyzed by qRT-PCR.

Expression of Immune Checkpoints in Malignant Tumors: Therapy Targets and Biomarkers for the Gastric Cancer Prognosis.

To increase the effectiveness of anticancer therapy based on immune checkpoint (IC) inhibition, some ICs are being investigated in addition to those used in clinic. We reviewed data on the relationship between PD-L1, B7-H3, B7-H4, IDO1, Galectin-3 and -9, CEACAM1, CD155, Siglec-15 and ADAM17 expression with cancer development in complex with the results of clinical trials on their inhibition. Increased expression of the most studied ICs-PD-L1, B7-H3, and B7-H4-is associated with poor survival; their inhibition is clinically significant.

Aberrant Methylation of 21 MicroRNA Genes in Breast Cancer: Sets of Genes Associated with Progression and a System of Markers for Predicting Metastasis.

Systemic analysis of the relationship between the levels of methylation of 21 microRNA genes and the parameters of breast cancer progression was performed on a representative sample of 91 paired specimens of breast cancer and histologically normal tissues and a system of markers for prediction of metastasis was proposed. A significant association of hypermethylation of 11 genes with late (III-IV) clinical stages was found, and for 6 genes (MIR124-1, MIR127, MIR34B/C, MIR9-3, MIR1258, and MIR339) this association was highly significant (p≤0.001, FDR=0.

LncRNAs in the Regulation of Genes and Signaling Pathways through miRNA-Mediated and Other Mechanisms in Clear Cell Renal Cell Carcinoma.

The fundamental novelty in the pathogenesis of renal cell carcinoma (RCC) was discovered as a result of the recent identification of the role of long non-coding RNAs (lncRNAs). Here, we discuss several mechanisms for the dysregulation of the expression of protein-coding genes initiated by lncRNAs in the most common and aggressive type of kidney cancer-clear cell RCC (ccRCC). A model of competitive endogenous RNA (ceRNA) is considered, in which lncRNA acts on genes through the lncRNA/miRNA/mRNA axis.

MiRNA Expression in Neuroendocrine Neoplasms of Frequent Localizations.

Neuroendocrine neoplasms (NEN) are infrequent malignant tumors of a neuroendocrine nature that arise in various organs. They occur most frequently in the lungs, intestines, stomach and pancreas. Molecular diagnostics and prognosis of NEN development are highly relevant.

The Choice of Candidates in Survival Markers Based on Coordinated Gene Expression in Renal Cancer.

We aimed to identify and investigate genes that are essential for the development of clear cell renal cell carcinoma (ccRCC) and sought to shed light on the mechanisms of its progression and create prognostic markers for the disease. We used real-time PCR to study the expression of 20 genes that were preliminarily selected based on their differential expression in ccRCC, in 68 paired tumor/normal samples. Upon ccRCC progression, seven genes that showed an initial increase in expression showed decreased expression.

Expansion of EasyClone-MarkerFree toolkit for Saccharomyces cerevisiae genome with new integration sites.

Biotechnological production requires genetically stable recombinant strains. To ensure genomic stability, recombinant DNA is commonly integrated into the genome of the host strain. Multiple genetic tools have been developed for genomic integration into baker's yeast Saccharomyces cerevisiae.

MicroRNA in Gastric Cancer Development: Mechanisms and Biomarkers.

Gastric cancer (GC) is one of the most common and difficult diseases to treat. The study of signaling pathway regulation by microRNA provides information on the mechanisms of GC development and is the basis for biomarker creation. In this study, a circuit of microRNA interactions with signaling pathways was constructed.

Preparation for the next COVID-19 wave: The European Hip Society and European Knee Associates recommendations.

Purpose: To plan for the continuance of elective hip and knee arthroplasty during a resurgence or new wave of COVID-19 infections.

Method: A systematic review was conducted using the terms "COVID-19" or "SARS-Cov-2" and "second wave". No relevant citations were found to inform on recommendations the plan.

A Group of miRNA as Candidates for Prognostic Biomarkers of Gastric Cancer Metastasis.

An association was found between reduced expression of miR-34a, miR-146a with both metastasis to regional lymph nodes (relative risk RR=10.50 and RR=5.25, respectively) and the development of distant metastases (RR=9.

System of Markers Based on the Methylation of a Group of Proapoptotic Genes in Combination with MicroRNA in the Diagnosis of Breast Cancer.

Systems of markers for the diagnosis of breast cancer based on DNA methylation of a group of suppressor protein-coding genes, hypermethylated microRNA genes, and their combinations were compiled. On a representative sample of 70 paired breast cancer specimens (tumor/normal), MS-PCR analysis revealed a significant increase in the methylation frequency of 5 protein-coding genes: RASSF1A suppressor and apoptosis genes APAF1, BAX, BIM/BCL2L11, and DAPK1 (34-61% vs. 4-24%) and 6 microRNA genes: MIRG124G1, MIRG125bG1, MIRG129G2, MIRG148a, MIRG34b/c, and MIRG9G3 (36-76% vs.

The Genes-Candidates for Prognostic Markers of Metastasis by Expression Level in Clear Cell Renal Cell Cancer.

The molecular prognostic markers of metastasis are important for personalized approaches to clear cell renal cell carcinoma (ccRCC) treatment but markers for practical use are still missing. To address this gap we studied the expression of ten genes-, , , , , , , , , and FN1-through RT-PCR, in 56 ccRCC patients without metastases and with metastases. All of these, excluding , showed differential and increased (besides ) expression in non-metastasis tumors.

Association of Target Therapy Gene Expression with Metastasizing of Clear-Cell Renal Cell Carcinoma.

We analyzed association of the levels of VEGFA, RAF1, and mTOR gene expression in the tissue of clear-cell renal cell carcinoma (ccRCC) with tumor metastasizing. Significant association with metastases was found only for VEGFA gene: OR=6.641, 95%CI=2.

Expression Profiles of Genes-Potential Therapy Targets-and Their Relationship to Survival in Renal Cell Carcinoma.

The main mechanisms of pathogenesis of clear cell renal cell carcinoma (CCRCC) are realized through the PI3K-AKT-mTOR and Ras-RAF-ERK signaling pathways. Targeted therapy is directed primarily at the genes and their encoded products that are components of these pathways. The levels of expression and coexpression of target genes were determined, and the difference in the functioning of the genes of one of the two major signaling pathways in tumors of CCRCC patients with different life duration (more and less than 3.

[Methylation of the genes for the microRNAs miR-129-2 and miR-9-1, changes in their expression, and activation of their potential target genes in clear cell renal cell carcinoma].

Methylation of promoter CpG islands and microRNA (miRNA) interactions with mRNAs of target genes are epigenetic mechanisms that play a crucial role in deregulation of gene expression and signaling pathways in tumors. Altered expression of six chromosome 3p genes (RARB(2), SEMA3B, RHOA, GPX1, NKIRAS1, and CHL1) and two miRNA genes (MIR-129-2 and MIR-9-1) was observed in primary clear cell renal cell carcinomas (ccRCCs, 31-48 samples) by RT-PCR and qPCR. Significant downregulation (p < 0.

[The hyper-methylated genes microRNA as potential markers of clear-cell carcinoma of kidney].

The clear-cell carcinoma of kidney is characterized by high rate of lethal outcomes. The lethality makes up to 16% in the first year after disease was diagnosed. The absence of efficient diagnostic at early stages (30% of all cases of clear-cell carcinoma of kidney are found out at late stages if there is metastatic disease) indicates the necessity of searching new biomarkers of clear-cell carcinoma of kidney.

[Molecular genetics study of hereditary predisposition to diffuse gastric cancer in Russian patients].

About 3% of cases of gastric cancer (GC) cases are due to hereditary predisposition. Molecular causes of inherited predisposition to diffuse GC among Russian patients have not been studied. In the present work there was performed the molecular genetics study in 9 probands with signet-ring cell GC.