Specificity of RNAi to selected target is challenged by off-target effects, both canonical and non-canonical. Notably, more than half of all human microRNAs are co-expressed with hosting them proteincoding genes. Here we dissect regulatory subnetwork centered on IGFBP6 gene, which is associated with low proliferative state and high migratory activity of basal-like breast cancer. We inhibited expression of IGFBP6 gene in a model cell line for basal-like breast carcinoma MDA-MB-231, then traced secondary and tertiary effects of this knockdown to LAMA4, a laminin encoding gene that contributes to the phenotype of triple-negative breast cancer. LAMA4-regulating miRNA miR-4274 and its host gene SORCS2 were highlighted as intermediate regulators of the expression levels of LAMA4, which correlated in a basal-like breast carcinoma sample subset of TCGA to the levels of SORCS2 negatively. Overall, our study points that the secondary and tertiary layers of regulatory interactions are certainly underappreciated. As these types of molecular event may significantly contribute to the formation of the cell phenotypes after RNA interference based knockdowns, further studies of multilayered molecular networks affected by RNAi are warranted.

In this literature review, the analysis of the studies of venous blood flow pathology in the inferior Vena cava system using magnetic resonance imaging (MRI) is carried out. Special attention is paid to the attempts made to use this method in the diagnosis of chronic lower limb vein disorders (CVD) through magnetic resonance venography (MRV). Historically and methodically, the gradual introduction of MRV methods in the diagnosis of lower limb vein thrombosis (LEDVT) and venous thromboembolism (VTE) has been shown.Methods of non-contrast MRV based on the effect of blood flow, as in the case of MR-Angiography, are divided into two principal groups: methods based on the amplitude effects of Time-of-Flight (TOF) and methods based on Phase Contrast effects (PC). Techniques for conducting contrast-free MRV are described in detail. Attention is paid to pulse sequences used in the world for visualization of veins in contrast-free MRV in TOF and PC mode (FR-FBI, SPADE, SSFP) and post-processing methods: 2D-TOF MRV FLASH, 2D-TOF MRV CRASS, FIPS, VED, VENS.Contrast-enhanced MRV (CE MRV) is based on the use of “blood pool” contrast agents, which feature the ability to form stable compounds with blood plasma proteins. Worldwidesubstances with magnetic and supermagnetic properties based on gadolinium or iron oxide are used as contrast agents for CE MRV. The result of using these contrast agents is an increase in the quality of visualization due to a better signal to noise ratio (SNR) using 3D image processing (3D CE MRV) using fast sequences: GRE, TFLAS, VESPA, CAT, in conditions of direct and indirect CE MRV.It is noted that in recent years, certain restrictions have been imposed on certain linear contrast agents containing gadolinium in their further use. Therefore, for the purpose of CE MRV, it is efficientl to use only cyclic contrast agents to avoid unnecessary risks.Contrast-free MRV has again received intensive development in recent years, due to the restrictions imposed, one of these methods is direct thrombus imaging (Direct Thrombus Imaging – DTI or Magnetic Resonance Direct Thrombus Imaging - MRDTI) using fast pulse sequences: bSSFP, BBTI, DANTE. The latest research on this LEDVT diagnostic method was published in 2019 and has shown high diagnostic value.For all the most commonly used methods of MRV, specificity and sensitivity are shown.Further MRV in patients with CVD and DVT is a promising diagnostic task in modern phlebology. MRV should be introduced into clinical practice more actively than it is today.

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