MicroRNA - Volume 13, Issue 2, 2024

MicroRNAs are a class of regulatory, non-coding small ribonucleic acid (RNA) molecules found in eukaryotes. Dysregulated expression of microRNAs can lead to downregulation or upregulation of their target gene. In general, microRNAs bind with the Argonaute protein and its interacting partners to form a silencing complex. This silencing complex binds with fully or partial complementary sequences in the 3’-UTR of their cognate target mRNAs and leads to degradation of the transcripts or translational inhibition, respectively. However, recent developments point towards the ability of these microRNAs to bind to the promoters, enhancers or coding sequences, leading to upregulation of their target genes. This review briefly summarizes the various non-canonical binding sites of microRNAs and their regulatory roles in various diseased conditions.

Non-coding RNAs that are small in size, called microRNAs (miRNAs), exert a consequence in neutralizing gene activity after transcription. The nervous system is a massively expressed organ, and an expanding body of research reveals the vital functions that miRNAs play in the brain's growth and neural activity. The significant benefit of miRNAs on the development of the central nervous system is currently shown through new scientific methods that concentrate on targeting and eradicating vital miRNA biogenesis pathways the elements involving Dicer and DGCR8. Modulation of miRNA has been associated with numerous essential cellular processes on neural progenitors, like differentiation, proliferation, and destiny determination. Current research discoveries that emphasize the significance of miRNAs in the complex process of brain development are included in this book. The miRNA pathway plays a major role in brain development, its operational dynamics, and even diseases. Recent studies on miRNA-mediated gene regulation within neural discrepancy, the circadian period and synaptic remodeling are signs of this. We also discussed how these discoveries may affect our comprehension of the fundamental processes behind brain diseases, highlighting the novel therapeutic opportunities miRNAs provide for treating various human illnesses.

Due to its non-invasive nature and easy accessibility, urine serves as a convenient biological fluid for research purposes. Furthermore, urine samples are uncomplicated to preserve and relatively inexpensive. MicroRNAs (miRNAs), small molecules that regulate gene expression post-transcriptionally, play vital roles in numerous cellular processes, including apoptosis, cell differentiation, development, and proliferation. Their dysregulated expression in urine has been proposed as a potential biomarker for various human diseases, including bladder cancer. To draw reliable conclusions about the roles of urinary miRNAs in human diseases, it is essential to have dependable and reproducible methods for miRNA extraction and profiling. In this review, we address the technical challenges associated with studying urinary miRNAs and provide an update on the current technologies used for urinary miRNA isolation, quality control assessment, and miRNA profiling, highlighting both their advantages and limitations.

Introduction: Numerous genetic and biological processes have been linked to the function of microRNAs (miRNAs), which regulate gene expression by targeting messenger RNA (mRNA). It is commonly acknowledged that miRNAs play a role in the development of disease and the embryology of mammals. Method: To further understand its function in the oncogenic process, the expression of the miRNA profile in cancer has been investigated. Despite being referred to as a noteworthy miRNA in cancer, it is unknown whether hsa-miR-1225-5p plays a part in the in vitro progression of the luminal A and luminal B subtypes of breast cancer. We proposed that a synthetic hsa-miR-1225-5p molecule be expressed in breast cancer cell lines and its activity be evaluated with the aim of studying its function in the development of luminal breast cancer. In terms of the typical cancer progression stages, such as proliferation, survival, migration, and invasion, we investigated the role of hsa-miR-1225-5p in luminal A and B breast cancer cell lines. Results: Additionally, using bioinformatics databases, we thoroughly explored the target score-based prediction of miRNA-mRNA interaction. Our study showed that the expression of miR-1225-5p significantly inhibited the in vitro growth of luminal A and B breast cancer cell lines. Conclusion: The results were supported by a bioinformatic analysis and a detailed gene network that boosts the activation of signaling pathways required for cancer progression.

Objectives: Periodontal diseases are a rather complex problem of modern dentistry and do not have only medical but also social significance. The objective of this study is to weigh the effect of a mixture of Thiotriazoline and L-arginine (1:4) on the parameters of the system of endogenous cytoprotection of blood and periodontal illness in rats with experimental chronic generalized periodontitis and substantiate further study of this blend. Materials and Methods: The study aimed to evaluate the impact of a combination of Thiotriazoline and L-arginine (in a ratio of 1:4) on the parameters of the endogenous blood cytoprotection system and periodontium in rats with experimental chronic generalized periodontitis. A group of outbred rats weighing 190-220 g and sourced from the vivarium of the Institute of Pharmacology and Toxicology of the Academy of Medical Sciences of Ukraine were divided into four groups, each consisting of 10 animals. (1) Intact group, animals that were injected intragastrically with a solution of sodium chloride to chloride 0.9% for 30 days. (2) control, animals with experimental CGP who intragastrically sodium chloride solution 0.9% for 30 days. (3) animals with experimental CGP were injected intramuscularly with Thiotriazoline + L-arginine (1:4) in a dosage of 200 mg/kg (30 days). (4) animals with experimental CGP, for which daily intragastric reference drug Mexidol, in dosage 250 mg/kg (30 days). In this study, we utilized two substances: Thiotriazoline and L-arginine hydrochloride. The combination of Thiotriazoline and L-arginine (in a ratio of 1:4) was prepared at the Department of Pharmaceutical Chemistry of ZSMU. At the conclusion of the experiment, the rats were carefully removed from the study while under thiopental-sodium anesthesia, and administered at a dosage of 40 mg/kg. Results: We have found that the administration of a combined preparation of Thiotriazoline with L-arginine to rats with CGP leads to a significant decrease in the blood concentration of pro-inflammatory cytokines IL-1b and TNF-a by 56.1% and 71%, respectively. Conclusion: The administration of Mexidol at a dosage of 250 mg/kg, as well as the combination of Thiotriazoline and Larginine in a ratio of 1:4 at a dosage of 200 mg/kg, resulted in a significant reduction in gingival pocket depth in animals with CGP. Specifically, the gingival pocket depth was reduced to 6 mm (p < 0.05) with Mexidol and further reduced to 4 mm (p < 0.05) with the combination of Thiotriazoline and L-arginine. Additionally, the animals exhibited minimal bleeding, swelling, and tooth mobility when treated with the combination of Thiotriazoline and L-arginine. The administration of a combination of Thiotriazoline and L-arginine (in a ratio of 1:4) at a dosage of 200 mg/kg to animals with CGP resulted in a noteworthy reduction in the blood concentration of pro-inflammatory cytokines IL-1b and TNF-a. Specifically, there was a significant decrease of 56.1% (p < 0.05) in IL-1b and 71% (p < 0.05) in TNF-a levels. The course administration of a combination of Thiotriazoline and L-arginine (1:4) (200 mg/kg) to animals with CGP led to an increased expression of HSP70 mRNA (p < 0.05) in the periodontium by 8.2 times and HIF-1a mRNA by 8.2 times. 2.8 times (p < 0.05) against the background of an increase in the blood concentration of HSP70 by 95% (p < 0.05). Also, in the periodontium of animals in this group, a decrease in the expression of c-Fos mRNA by 36.7% (p < 0.05) was found compared to the control group.

Background: The COG complex is implicated in the tethering of retrograde intra-Golgi vesicles, which involves vesicular tethering and SNAREs. SNARE complexes mediate the invasion and metastasis of cancer cells through MMPs which activate growth factors for ECM fragments by binding to integrin receptors. Increasing MMPs is in line with YKL40 since YKL40 is linked to promoting angiogenesis through VEGF and can increase ovarian cancer (OC) resistance to chemotropic and cell migration. Objective: The aim of this study is an assessment of siRNA-COG3 on proliferation, invasion, and apoptosis of OC cells. In addition, siRNA-COG3 may prevent the growth of OC cancer in mice with tumors. Methods: Primary OC cell lines will be treated with siRNA-COG3 to assay YKL40 and identified angiogenesis by Tube-like structure formation in HOMECs. The Golgi morphology was analyzed using Immunofluorescence microscopy. Furthermore, the effects of siRNA-COG3 on the proliferation and apoptosis of cells were evaluated using MTT and TUNEL assays. Clones of the HOSEpiC OC cell line were subcutaneously implanted in FVB/N mice. Mice were treated after two weeks of injection of cells using siRNA-COG3. Tumor development suppression was detected by D-luciferin. RT-PCR and western blotting analyses were applied to determine COG3, MT1- MMP, SNAP23, and YKL40 expression to investigate the effects of COG3 gene knockdown. Results: siRNA-COG3 exhibited a substantial effect in suppressing tumor growth in mice. It dramatically reduced OC cell proliferation and triggered apoptosis (all p < 0.01). Inhibition of COG3, YKL-40, and MT1-MPP led to suppression of angiogenesis and reduction of microvessel density through SNAP23 in OC cells. Conclusion: Overall, by knockdown of the COG3 gene, MT1-MMP and YKL40 were dropped, leading to suppressed angiogenesis along with decreasing migration and proliferation. SiRNACOG3 may be an ideal agent to consider for clinical trial assessment therapy for OC, especially when an antiangiogenic SNAR-pathway targeting drug.

Background: Long non-coding RNA (lncRNA) plays a crucial role in various biological processes, and mutations or imbalances of lncRNAs can lead to several diseases, including cancer, Prader-Willi syndrome, autism, Alzheimer's disease, cartilage-hair hypoplasia, and hearing loss. Understanding lncRNA-protein interactions (LPIs) is vital for elucidating basic cellular processes, human diseases, viral replication, transcription, and plant pathogen resistance. Despite the development of several LPI calculation methods, predicting LPI remains challenging, with the selection of variables and deep learning structure being the focus of LPI research. Methods: We propose a deep learning framework called AR-LPI, which extracts sequence and secondary structure features of proteins and lncRNAs. The framework utilizes an auto-encoder for feature extraction and employs SE-ResNet for prediction. Additionally, we apply transfer learning to the deep neural network SE-ResNet for predicting small-sample datasets. Results: Through comprehensive experimental comparison, we demonstrate that the AR-LPI architecture performs better in LPI prediction. Specifically, the accuracy of AR-LPI increases by 2.86% to 94.52%, while the F-value of AR-LPI increases by 2.71% to 94.73%. Conclusion: Our experimental results show that the overall performance of AR-LPI is better than that of other LPI prediction tools.