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. The microRNAs, associated with metastasis and chemoresistance, are described. In most cases, microRNAs in GC regulate the Wnt/β-catenin, PI3K/AKT/mTOR, RAS/RAF/ERK/MAPK, NF-kB, TGF-β, and JAK/STAT pathways. Part of the microRNA acts on several target genes that function in different pathways. This often leads to an intensification of the induced processes. MicroRNAs have also been described that have the opposite effect on different pathways, causing different functional consequences. By acting on several target genes, or genes associated with several pathways, microRNAs can function in a signaling network. MicroRNAs associated with metastasis most often interact with the Wnt/β-catenin pathway. MicroRNAs affecting chemoresistance, in most cases, affect the regulators of apoptosis and are associated with the PI3K/AKT/mTOR pathway. The characteristics of microRNAs proposed as candidates for GC biomarkers were analyzed. The currently developed diagnostic and prognostic panels of microRNAs are also considered.

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. An important feature of miRNA is its ability to affect the expression of several genes simultaneously, which corresponds to the trend toward the use of combination therapy. The article provides a list of miRNAs acting simultaneously on several ICs and miRNAs that, in addition to IC, can regulate the expression of targeted therapy genes. There is dependence of miRNA interactions with IC genes on the type of cancer. The analysis of the accumulated data demonstrates that only about 14% (95% CI: 9.8–20.1%) of the studied miRNAs regulate the expression of specific IC in more than one type of cancer. That is, there is tumor specificity in the miRNA action on ICs. A number of miRNAs demonstrated high efficiency in vitro and in vivo. This indicates the potential of miRNAs as promising agents for cancer immunotherapy. Additional studies of the miRNA–gene interaction features and the search for an optimal miRNA mimic structure are necessary.

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. For the most studied oncogenic lncRNAs, such as HOTAIR, MALAT1, and TUG1, several regulatory axes were identified in ccRCC, demonstrating a number of sites for various miRNAs. Interestingly, the LINC00973/miR-7109/Siglec-15 axis represents a novel agent that can suppress the immune response in patients with ccRCC, serving as a valuable target in addition to the PD1/PD-L1 pathway. Other mechanisms of action of lncRNAs in ccRCC, involving direct binding with proteins, mRNAs, and genes/DNA, are also considered. Our review briefly highlights methods by which various mechanisms of action of lncRNAs were verified. We pay special attention to protein targets and signaling pathways with which lncRNAs are associated in ccRCC. Thus, these new data on the different mechanisms of lncRNA functioning provide a novel basis for understanding the pathogenesis of ccRCC and the identification of new prognostic markers and targets for therapy.

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 (MIR107, MIR124-2, MIR124-3, MIR125B-1, MIR127, MIR129-2, MIR130B, MIR132, MIR193A, MIR339, MIR34B/C, MIR9-1, and MIR9-3) were hypermethylated already at the early stages of OvCa, while hypermethylation of MIR1258, MIR137, MIR203A, and MIR375 was pronounced in metastatic tumors, and MIR148A 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. Moreover, expression levels of six miRNAs were significantly decreased in metastatic tumors in comparison with nonmetastatic ones, and downregulation of miR-203a-3p was the most significant. We revealed an inverse relationship between expression levels of miR-203a-3p and those of ZEB1 and ZEB2 genes, which are EMT drivers. We also identified three miRNA genes (MIR148A, MIR9-1, and MIR193A) that likely regulate EMT–MET reversion in the colonization of PMM. According to the Kaplan–Meier analysis, hypermethylation of several examined miRNA genes was associated with poorer overall survival of OvCa patients, and high methylation levels of MIR130B and MIR9-1 were related to the greatest relative risk of death.

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 role of clinical biomarkers can be played by microRNAs (miRNAs). This work is devoted to the analysis of data on miRNA expression in NENs. For the first time, a search for specificity or a community of their functional characteristics in different types of NEN was carried out. Their properties as biomarkers were also analyzed. To date, more than 100 miRNAs have been characterized as differentially expressed and significant for the development of NEN tumors. Only about 10% of the studied miRNAs are expressed in several types of NEN; differential expression of the remaining 90% was found only in tumors of specific localizations. A significant number of miRNAs have been identified as potential biomarkers. However, only a few miRNAs have values that characterized their quality as markers. The analysis demonstrates the predominant specific expression of miRNA in each studied type of NEN. This indicates that miRNA’s functional features are predominantly influenced by the tissue in which they are formed.

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—CA9, NDUFA4L2, VWF, IGFBP3, BHLHE41, EGLN3, SAA1, CSF1R, C1QA, and FN1—through RT-PCR, in 56 ccRCC patients without metastases and with metastases. All of these, excluding CSF1R, showed differential and increased (besides SAA1) expression in non-metastasis tumors. The gene expression levels in metastasis tumors were decreased, besides CSF1R, FN1 (not changed), and SAA1 (increased). There were significant associations of the differentially expressed genes with ccRCC metastasis by ROC analysis and the Fisher exact test. The association of the NDUFA4L2, VWF, EGLN3, SAA1, and C1QA expression with ccRCC metastasis is shown for the first time. The CA9, NDUFA4L2, BHLHE4, and EGLN3 were distinguished as the strongest candidates for ccRCC metastasis biomarkers. We used an approach that presupposed that the metastasis marker was the expression levels of any three genes from the selected panel and received sensitivity (88%) and specificity (73%) levels with a relative risk of RR > 3. In conclusion, a panel of selected genes—the candidates in biomarkers of ccRCC metastasis—was created for the first time. The results might shed some light on the ccRCC metastasis processes.