ABSTRACT
Hemorrhagic fever with renal syndrome (HFRS) is an acute natural focal viral disease caused by viruses of the genus hantavirus, characterized by damage to small blood vessels, kidneys, lungs and other organs of a person. MicroRNAs (miRNAs) are 18-22 nucleotide endogenously expressed RNA molecules that inhibit gene expression at the post-transcriptional level by binding to the 3-untranslated region of the target mRNA. It has been proven that miRNAs play a significant role in various biological processes, including the cell cycle, apoptosis, cell proliferation and differentiation. It has been proven that miRNAs may be involved in the pathogenesis of infectious diseases, including HFRS. Hantavirus infection predominantly affects endothelial cells and causes dysfunction of the endothelium of capillaries and small vessels. It is known that the immune response induced by Hantavirus infection plays an important role in disrupting the endothelial barrier. In a few studies, both in vitro and in vivo, it has been shown that endothelial dysfunction and the immune response after infection with Hantavirus can be partially regulated by miRNAs by acting on certain genes. Most of the miRNAs is expressed within the cells themselves. However, in some biological fluids of the human body, for example, plasma or blood serum, numerous miRNAs, called circulating miRNAs, have been found. Circulating miRNAs can be secreted by cells into human biological fluids as part of extracellular vesicles as exosomes or be part of an RNA-bound protein complex as miRNA-Argonaute 2 (Ago2). These miRNAs are resistant to nucleases, which makes them attractive as potential biomarkers in various human diseases. There is no specific antiviral therapy for HFRS, and the determination of laboratory parameters that are used to diagnose, assess the severity, and predict the course of the disease remains a challenge due to the peculiarities of the pathophysiology and clinical course of the disease. Studying the role of miRNAs in HFRS seems to be expedient for the development of specific and effective therapy, as well as for use as diagnostic and prognostic biomarkers (in relation to circulating miRNAs).
Subject(s)
Hemorrhagic Fever with Renal Syndrome , MicroRNAs , Orthohantavirus , Endothelial Cells , Orthohantavirus/genetics , Hemorrhagic Fever with Renal Syndrome/genetics , Humans , Kidney , MicroRNAs/geneticsABSTRACT
Spinal cord injury (SCI) may be followed by persistent motor dysfunction and somatosensory disturbances that negatively influences the quality of life of patients and creates a significant economic burden. Analysis of secondary biological processes associated with changes in genetic expression is becoming increasingly important every day in understanding the pathophysiology of spinal cord injury. The results of international sequencing of the human genome were analyzed in 2004. These data revealed about 20,000 protein-coding genes covering near 2% of the total genomic sequence. The vast majority of gene transcripts are actually characterized as non-coding RNAs (ncRNAs). These RNA clusters do not encode functional proteins and ensure post-transcriptional regulation of gene expression. The clusters may be small (approximately 20 nucleotides) known as miRNAs or the transcripts can enroll over 200 nucleotides defined as long non-coding RNAs (lncRNAs). Some modern studies describe transient expression of microRNA in case of spinal cord injury. These RNAs are associated with inflammation and apoptosis, functional recovery and regeneration. Large-scale genomic analysis has demonstrated the existence of multiple lncRNAs whose expression is associated with some processes of spinal cord injury. lncRNA can be divided into two categories depending on the position in relation to the coding genes: intergenic and intragenic. Intergenic lncRNAs is currently the most studied class. Intragenic lncRNAs can be subdivided depending on the overlap of the coding genes (antisense, intron, etc.). According to recent studies, long non-coding RNAs are abundantly present in the tissues of central nervous system and may be crucial in the pathogenesis of certain diseases of nervous system. At the cellular level, it has been shown that lncRNAs regulate the expression of protein-coding RNAs. Moreover, these molecules are involved into such processes as neuronal death, demyelination and glia activation. This review is devoted to the role of ncRNAs in the pathogenesis of spinal cord injury and their potential use as targets for the treatment of consequences of spinal cord injury.
Subject(s)
RNA, Long Noncoding/genetics , Spinal Cord Injuries/therapy , Gene Expression Regulation , Humans , Quality of Life , RNA, UntranslatedABSTRACT
High-grade glial tumors (also called high-grade gliomas) are the most aggressive primary brain neoplasms. Therefore, much attention is paid to understanding the pathogenesis, as well as to the development of new effective diagnostic and therapeutic methods. MicroRNAs are short non-coding RNAs, 18-22 nucleotides in length, which, as has already been shown, play a direct role in carcinogenesis. Circulating miRNAs are released into the extracellular space and can be in a stable state for a long time in most biological liquids, including blood serum and plasma. Circulating miRNAs are promising biomarkers with different expression profiles specific for various human disorders, including cancer diseases.There are many data showing that different profiles of circulating miRNAs, in particular in extracellular vesicles (EV), in human biological fluids are associated with numerous neoplastic processes, which indicates that miRNAs can be a truly new class of biomarkers for early diagnosis and prognosis of high-grade gliomas.
