Extrinsic pathway12/17/2023 The most well studied CD95 receptor is (Fas/APO-1). If the aberrant expression of such onco-miRNAs is associated with early HCC recurrence and poor patient outcome, these miRNAs are of interest for use as biomarkers and therapeutic targets.Īs a promising target for the development of new anticancer drugs, the inexternal pathway of apoptosis induced through cell death receptors, a separate a subgroup of the tumor necrosis factor (TNF) receptor family (see review ), is of interest. It should be noted that in the context of the development and progression of malignant tumors, miRNAs targeted to tumor suppressor genes function as oncogenes. From this point of view, of greatest interest are miRNAs whose high or low expression is associated with tumor proliferation. The use of miRNA mimetics and inhibitors, which play a significant role in the regulation of the expression of target genes involved in the pathogenesis of HCC, may be decisive. In this regard, an individual, patient-oriented approach is important. HCC, which has a high recurrence rate and low five-year survival, is characterized by significant structural and interindividual heterogeneity, which complicates diagnosis, prognosis, and response to treatment. Worldwide about 750 000 people die from HCC every year. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. In man miRNA expression disorders are associated with various diseases: allergic diseases, cardiovascular diseases, respiratory diseases, diabetes mellitus, bronchial asthma, and oncological diseases. The database hsa-miRTarBase ( ) has experimental data on the participation of more than 4000 different miRNAs in the regulation of the activity of more than 27 thousand target genes in 37 species. microRNAs are involved in the regulation of many processes, including development, differentiation, cell survival, and functioning of the immune system. MicroRNAs (miRNAs) are a class of small, endogenous, single-stranded, non-coding RNAs ~18–25 nucleotides in length that regulate the expression of their target genes through a variety of mechanisms, including mRNA degradation and translational inhibition through both direct binding to a complementary sequence in the 3'-untranslated region (3′UTR) mRNA and regulation of gene expression mediated by regulatory pathways. It is also shown that hsa-miR-373, hsa-miR-106b and hsa-miR-96 have the highest priority as markers of hepatocellular carcinoma, whose action on secondary targets enhances their anti-apoptotic effect. The potential effect of hsa-miRNAs mediated by action on secondary targets is shown to negatively correlate with the number of primary targets. For these hsa-miRNAs, using the software package ANDSystem, we reconstructed the regulation of the expression of secondary targets and analyzed their impact on the activity of the extrinsic pathway of apoptosis. Their aberrant expression is associated with early disease relapse and poor patient outcome. The present work summarizes data on hsa-miRNAs whose primary targets are key genes of the extrinsic pathway of apoptosis. While the former are actively studied, the role of secondary targets of these hsa-miRNAs in modulating apoptosis is still unclear. However, the effect of hsa-miRNA on tumor development depends not only on its direct effect on expression of genes, the primary targets, but also on secondary targets mediated by regulatory pathways. From this point of view hsa-miRNAs are of interest, their aberrant expression is associated with poor prognosis for patients and is associated with tumor progression due to dysregulation of programmed cell death (apoptosis). In this regard, an individualized, patient-centered approach becomes important, in which the use of mimetics and hsa-miRNA inhibitors involved in the pathogenesis of the disease may be determinative. It is very heterogeneous both in structure and between patients, which complicates the diagnosis, prognosis and response to treatment. Abstract-One of the most common malignant liver diseases is hepatocellular carcinoma, which has a high recurrence rate and a low five-year survival rate.
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