E. A. Bogomolova’s research while affiliated with Russian Academy of Sciences and other places

The MPC 1 gene is involved in the transport of pyruvate into mitochondria, playing an important role in metabolic processes. Recently, it has been reported that higher MPC 1 expression correlates with an increased number of immune cells in human cervical and lung cancers, indicating an enhanced antitumor immune response. Reduced MPC 1 levels in gastric tumors are associated with a more severe disease course. Correlational analysis of the MPC 1 gene in human lung, hippocampus and frontal cortex tissue samples based on data from the GTEx database revealed associations of this gene with schizophrenia, non-small cell lung cancer, and immune diseases. Our experiments showed that the mRNA level of the MPC 1 gene in the non-small cell lung cancer cell line A549 increases 5-fold under the influence of the schizophrenia neuroleptic thioridazine. The observed elevation of MPC 1 level may cause tumor infiltration by immune cells, complementing the previously reported data indicating the ability of thioridazine to slow cell growth, induce apoptosis and reduce the ability of cells to migrate.

An inhibitor of the complement system CD55/DAF is expressed on many cell types. Dysregulation of CD55 expression is associated with increased disease severity during influenza A infection, as well as with vascular complications in pathologies involving excessive activation of the complement system. Using a luciferase reporter system, we performed functional analysis of the single nucleotide polymorphism rs2564978 located in the promoter of the CD55 gene in human pro-monocytic cell line U937. We have shown a decreased activity in activated U937 cells of the CD55 gene promoter carrying minor rs2564978(T) allele associated with the severe course of influenza A(H1N1)pdm09. Using bioinformatic resources, we determined that transcription factor PU.1 can potentially bind to the CD55 promoter region containing rs2564978 in an allele-specific manner. The involvement of PU.1 in modulating CD55 promoter activity was determined by genetic knockdown of PU.1 using small interfering RNAs under specific monocyte activation conditions.

Interleukin 10 (IL10) is a major anti-inflammatory cytokine that acts as a master regulator of the immune response. A single nucleotide polymorphism rs3024505(C/T), located downstream of the IL10 gene, is associated with several aggressive inflammatory diseases, including systemic lupus erythematosus, Sjögren’s syndrome, Crohn’s disease, and ulcerative colitis. In such autoimmune pathologies, IL10-producing B cells play a protective role by decreasing the level of inflammation and restoring immune homeostasis. This study demonstrates that rs3024505 is located within an enhancer that augments the activity of the IL10 promoter in a reporter system based on a human B cell line. The common rs3024505(C) variant creates a functional binding site for the transcription factor STAT3, whereas the risk allele rs3024505(T) disrupts STAT3 binding, thereby reducing the IL10 promoter activity. Our findings indicate that B cells from individuals carrying the minor rs3024505(T) allele may produce less IL10 due to the disrupted STAT3 binding site, contributing to the progression of inflammatory pathologies.

The transcription factor STAT3 serves as an immunoregulator by playing a crucial role in cytokine receptor signaling. However, in various cancer cell types, STAT3 is involved in the molecular mechanisms of oncogenesis. Specifically, in glioblastoma, the STAT3 immunoregulator has been linked to resistance to temozolomide, the most commonly used chemical agent for treating this type of cancer. Furthermore, literature suggests that activation of this oncogene in glioblastoma cells can significantly impact the tolerogenic tumor microenvironment, weakening the antitumor immune response and contributing to the aggressive course of the disease. Therefore, suppressing STAT3 may not only affect cell growth and resistance to chemotherapy but also enhance the immune response by improving the tumor microenvironment. The development of sequencing technologies has revealed that most of the transcribed material in the cell is noncoding. Long non-coding RNAs are gaining popularity in the study of oncogenesis due to their functional role in the development of various diseases, including oncology. A subtype of long non-coding RNAs transcribed from enhancer elements, known as enhancer RNAs, has garnered attention due to their high specificity in various cells and tissues. Gene co-expression analysis in glioblastoma tumors showed a correlation between STAT3 expression and the enhancer RNA LINC00910, which is located in the same chromosomal domain as the Stat3 gene. Previous literature has shown that LINC00910 is associated with both colorectal and gastric cancer. Additionally, data from the GeneHancer database suggests that the enhancer RNA LINC00910 may be involved in regulating the STAT3 immunoregulator. RNA interference was used to effectively knockdown the enhancer RNA LINC00910, resulting in an 8- to 10-fold reduction in its expression in glioblastoma cell lines. The reduction of LINC00910 expression did not significantly affect Stat3 gene expression in glioblastoma cell lines DBTRG-05MG and U251. This suggests that the correlation between LINC00910 RNA expression and STAT3 gene expression is not due to LINC00910’s direct involvement in STAT3 gene regulation in these cells. Further studies using the selected interfering RNA will help to clarify the role of the enhancer RNA LINC00910 in other signallingsignaling pathways, as well as its potential relationship with cancer development.

A certain degree of chromatin openness is necessary for the activity of transcription-regulating regions within the genome, facilitating accessibility to RNA polymerases and subsequent synthesis of regulatory element RNAs (regRNAs) from these regions. The rapidly increasing number of studies underscores the significance of regRNAs across diverse cellular processes and diseases, challenging the paradigm that these transcripts are non-functional transcriptional noise. This review explores the multifaceted roles of regRNAs in human cells, encompassing rather well-studied entities such as promoter RNAs and enhancer RNAs (eRNAs), while also providing insights into overshadowed silencer RNAs and insulator RNAs. Furthermore, we assess notable examples of shorter regRNAs, like miRNAs, snRNAs, and snoRNAs, playing important roles. Expanding our discourse, we deliberate on the potential usage of regRNAs as biomarkers and novel targets for cancer and other human diseases.

The complement inhibitor CD55/DAF is expressed on many cell types. Dysregulation of CD55 expression is associated with increased disease severity in influenza A infection and vascular complications in pathologies that involve excessive activation of the complement system. A luciferase reporter system was used to functionally analyze the single nucleotide polymorphism rs2564978 in the U937 human promonocytic cell line. The polymorphism is in the promoter of the CD55 gene, and its minor allele T is associated with a severe course of influenza A(H1N1)pdm09. A decreased activity of the CD55 promoter carrying the minor rs2564978(T) allele was observed in activated U937 cells, which provide a cell model of human macrophages. Using bioinformatics resources, PU.1 was identified as a potential transcription factor that may bind to the CD55 promoter at the rs2564978 site in an allele-specific manner. The involvement of PU.1 in modulating CD55 promoter activity was verified by a PU.1 genetic knockdown with small interfering RNAs under specific monocyte activation conditions.