Researchers Find Therapeutic Targets to Fight SARS-CoV-2
Researchers from HSE University have developed new approaches for regulating the expression of ACE2 and TMPRSS2 enzymes, which play a crucial role in cell infection with SARS-CoV-2. The scholars discovered that small non-coding microRNA (miRNA) molecules are capable of performing a targeted decrease in ACE2 and TMPRSS2. The results of the study have been published in PLOS ONE journal.
Angiotensin-convertingenzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) enzymes act as entrance gates into the cell for the novel coronavirus. After successful penetration, the virus uses the cell’s recourses to replicate and exit the cell to infect new cells. Research teams all over the world are experimenting with medicinal impact on ACE2 and TMPRSS2 aimed at blocking opportunities for SARS-CoV-2 virus to enter human cells.
In addition, the ACE2 enzyme also plays a major role in the development of the acute respiratory distress syndrome, the main cause of death in patients with COVID-19. Apart from the respiratory organs, ACE2 and TMPRSS2 are also present in other parts of the body, such as the digestive system, kidneys and liver. This explains the variety of symptoms in patients, including gastrointestinal issues.
Stepan Nersisyan and Alexander Tonevitsky from the HSE Faculty of Biology and Biotechnology, together with their colleagues from Hertsen Moscow Oncology Research Center (Maxim Shkurnikov), Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS (Evgeny Knyazev) and German Cancer Research Center, Heidelberg (Andrey Turchinovich), looked at potential approaches for influencing the abovementioned enzymes via miRNA molecules.
They carried out bioinformatic analysis of publicly available datasets on RNA sequencing in tissues of ten key human organs. The main task was to find miRNAs, the expression of which would demonstrate a significant negative correlation with ACE2 and TMPRSS2 gene expression. This means that the more miRNA, the less ACE2/TMPRSS2, and vice versa. As a result, the researchers detected a certain amount of such interactions that are specific for several organs at the same time. In particular, they discovered that lysine-specific demethylase 5B (JARID1B) can indirectly affect ACE2/TMPRSS2 expression by repressing transcription of hsa-let-7e/hsa-mir-125a and hsa-mir-141/hsa-miR-200 miRNA families which are targeting these genes.
Stepan Nersisyan
International Laboratory of Microphysiological Systems: Junior Research Fellow
Alexander Tonevitsky
Dean of the Faculty of Biology and Biotechnology
See also:
Early Molecular Diagnosis of Cancer Proven More Cost-Effective Than Subsequent Treatment of Advanced Disease
Applying expensive diagnostic methods in clinical practice will ultimately cost society 5 to 10 times less than the expenditures associated with late-stage cancer treatment, including subsequent disability pensions and sick leave payments—these are the findings from a study conducted by researchers at the HSE Faculty of Economic Sciences Marina Kolosnitsyna and Anastasia Vladimirskaya in collaboration with colleagues at EVOGEN, a medical genetic laboratory, and the Department of Health of the Yamalo-Nenets Autonomous Okrug. The study results have been published in Social Aspects of Population Health.
Scientists Discover Cause of Metastasis Formation in Patients with Colorectal Cancer
An international team of researchers including scientists at the HSE Faculty of Biology and Biotechnology has identified factors which can increase the aggressiveness of tumours in patients with colorectal cancer. An isoform of CD44 protein has been found to play a pivotal role in the development of metastases. The study findings have been published in Molecular Oncology.
Scientists Have Developed a Model of Malignant Prostate Tumour and Used It to Test Drug Efficacy
Researchers from HSE University and the Russian Ministry of Health National Medical Research Radiological Centre have successfully generated a three-dimensional laboratory model of prostate cancer and used the model for testing an anti-tumour drug. In the future, this approach has the potential to significantly enhance the efficacy of cancer treatment for patients. The study’s findings have been published in Cancer Urology.
Nanai and Chukchi Found Intolerant to 'Mushroom Sugar'
A team of researchers from HSE University, the RAS Research Centre for Medical Genetics, and the Moscow State University Institute of Anthropology have examined the impact of the human genotype on the production of trehalase, an enzyme responsible for metabolising 'mushroom sugar'. The researchers examined 1,068 DNA samples collected from inhabitants of northern and Arctic regions of Russia and found that the overall risk of trehalase deficiency in certain indigenous northern populations can be as high as 60–70%. The paper has been published in Problems of Nutrition.
HSE Biologists Explain Mechanism behind Coronavirus Evolution
A team of researchers, including scientists of the HSE Faculty of Biology and Biotechnology, have analysed the evolutionary path of the coronavirus from the Wuhan variant to Omicron. Their findings indicate that many genomic mutations in SARS-CoV-2 are shaped by processes occurring in the intestines and lungs, where the virus acquires the ability to evade the inhibitory effects of microRNA molecules. The study findings have been published in the Journal of Medical Virology.
Conserved microRNAs and Flipons Shape Gene Expression
An international team, including researchers of the HSE Faculty of Computer Science, has discovered a new mechanism of gene regulation in which microRNA assumes a central role. These non-coding molecules influence the DNA regions within genes that govern embryonic development. The study contributes to our understanding of the mechanisms underlying the diverse genetic programs found in complex multicellular organisms. The paper has been published in the International Journal of Molecular Sciences.
Russian Researchers Explain Origins of Dangerous Coronavirus Variants
HSE researchers, in collaboration with their colleagues from Skoltech and the Central Research Institute for Epidemiology, have uncovered the mechanisms behind the emergence of new and dangerous coronavirus variants, such as Alpha, Delta, Omicron, and others. They have discovered that the likelihood of a substitution occurring at a specific site of the SARS-CoV-2 genome is dependent on concordant substitutions occurring at other sites. This explains why new and more contagious variants of the virus can emerge unexpectedly and differ significantly from those that were previously circulating. The study’s findings have been published in eLife.
Research Finds Genes Associated with Most Aggressive Kidney Cancer
HSE researchers have found genes characteristic of the most aggressive subtype of clear cell renal carcinoma. Having studied data on tumour samples from 456 patients, Grigory Puzanov, research fellow at the HSE Faculty of Computer Science International Laboratory of Bioinformatics, identified cancer subtypes associated with either a favourable or unfavourable course of the disease. The paper is published in Scientific Reports.
Microfluidic Chip Used to Test Drug Toxicity
A team including HSE researchers has developed a way to use microfluidic chips to assess the toxic effects of drugs on humans. This device will help identify and minimise the side effects of drugs during the preclinical trial stage and reduce the need for animal experiments. The study is published in Bulletin of Experimental Biology and Medicine.
Biologists Figure Out How Stem Cells Turn Into Other Types of Cells at Molecular Level
An international team of researchers including biologists from HSE University has developed a method that helps obtain information on changes in protein expression and properties during cells’ transition from one state to another. One of the most interesting transitions is the transformation of cells from undifferentiated stem cells to differentiated cells of various organs and tissues. The paper was published in Nature Communications.