MicroRNAs (miRs, miRNAs) are small molecules of 18–22 nucleotides that serve as important regulators of gene expression at the post-transcriptional level. One of the mechanisms through which miRNAs regulate gene expression involves the interaction of their “seed” sequences primarily with 3′-end and more rarely with 5′-end, of mRNA transcribed from target genes. Numerous studies over the past decade have been devoted to quantitative and qualitative assessment of miRNAs expression and have shown remarkable changes in miRNA expression profiles in various diseases. Thus, profiling of miRNA expression can be an important tool for diagnostics and treatment of disease. However, less attention has been paid towards understanding the underlying reasons for changes in miRNA expression, especially in cancer cells. The purpose of this review is to analyze and systematize current data that explains reasons for changes in the expression of miRNAs. The review will cover both transcriptional (changes in gene expression and promoter hypermethylation) and post-transcriptional (changes in miRNA processing) mechanisms of regulation of miRNA expression, as well as effects of endogenous (hormones, cytokines) and exogenous (xenobiotics) compounds on the miRNA expression. The review will summarize the complex multilevel regulation of miRNA expression, in relation to cell type, physiological state of the body and various external factors.

Tyrosine kinase inhibitor- (TKI-) based therapy revolutionized the overall survival and the quality of life in non-small-cell lung cancer (NSCLC) patients that have epidermal growth factor receptor (EGFR) mutations. However, EGFR is a highly polymorphic and mutation-prone gene, with over 1200 single nucleotide polymorphisms (SNPs). Since the role of EFGR polymorphism on the treatment outcome is still a matter of debate, this research analyzed the available literature data, according to the PRISMA guidelines for meta-analyses. Research includes PubMed, Scopus, ISI Web of Science, and 14 of genome-wide association studies (GWAS) electronic databases in order to provide quantitative assessment of the association between ten investigated EGFR SNPs and the survival of NSCLC patients. The pooled HR and their 95% CI for OS and PFS for different EGFR polymorphisms using a random or fixed effect model based on the calculated heterogeneity between the studies was applied. The longest and the shortest median OSs were reported for the homozygous wild genotype and a variant allele carriers for rs712829 (-216G>T), respectively. Quantitative synthesis in our study shows that out of ten investigated EGFR SNPs (rs11543848, rs11568315, rs11977388, rs2075102, rs2227983, rs2293347, rs4947492, rs712829, rs712830, and rs7809028), only four, namely, rs712829 (-216G>T), rs11568315 (CA repeat), rs2293347 (D994D), and rs4947492, have been reported to affect the outcome of TKI-based NSCLC treatment. Of these, only -216G>T and variable CA repeat polymorphisms have been confirmed by meta-analysis of available data to significantly affect OS and PFS in gefitinib- or erlotinib-treated NSCLC patients.

We estimated the frequency of CYP1A1, CYP1A2, CYP1B1, CYP19, and SULT1A1 allelic variants in a female population of the Novosibirsk district and their association with the elevated risk of breast (BC), ovarian (OC), and endometrial (EC) cancers. Significant differences (OR = 2.34, p = 0.0002) in the allele distributions for CYP1A1 M1 polymorphism between patients with BC (n = 118) and controls (n = 180) were found. No significant difference in both genotype and allele distributions for CYP1A1 polymorphisms in patients with OC (n = 96) and EC (n = 154) was observed. Remarkable differences in the allele and genotype distributions for CYP1A2*1F polymorphism in patients with BC or OC were found (OR = 0.26, p = 0.0000005 and OR = 0.34, p = 0.00000002). There were no differences for this polymorphism in women with EC. In patients with BC no significant differences were found in genotype and allele distributions for R264C polymorphism in the CYP19 gene. The frequency of a mutant CYP19 heterozygote genotype C/T was higher in patients with OC and EC compared with healthy women (OR = 3.87, p = 0.001 and OR = 3.73, p = 0.0004, respectively). Comparison of allele frequencies revealed a deficiency of an allele A of SULT1A1*2 in patients with OC (OR = 0.64, p = 0.019) compared with controls. No differences were found in the genotype and allele distributions for SULT1A1 polymorphism between patients with BC and EC and controls. In addition, there were no difference in allele and genotype distributions for CYP1B1 119G-->T polymorphism between BC and control. In conclusion, these results support the hypothesis that susceptibility gene alleles of estrogen-metabolizing enzymes may differentially influence risk for woman hormone-dependent cancers.

Constitutive androstane receptor (CAR, NR1I3), which is under consideration in this review, is a member of the superfamily of nuclear receptors. However, certain features distinguish CAR from the variety of nuclear receptors. First, this receptor has structural features that allow it to display constitutive activity in the absence of a ligand and to interact in a species-specific manner with a huge number of ligands diverse in chemical structure and origin. Second, recently many researchers are focused on CAR because the significance is increasingly shown of its influence on a variety of physiological functions, such as gluconeogenesis, metabolism of xenobiotics, fatty acids, bilirubin, and bile acids, hormonal regulation, etc. In addition to the fundamental scientific interest, the study of CAR is of practical importance because changes in CAR activity can lead to disorders in physiological processes, which finally can result in changes in pathological states. However, despite intensive studies, many mechanisms are still unclear, which makes it difficult to understand the role of CAR in the overall picture of molecular regulation of physiological processes. This review analyzes the features and diversity of the functions of CAR.