Use Of miRNAs Research Articles

Network Pharmacology Approaches Used to Identify Therapeutic Molecules for Chronic Venous Disease Based on Potential miRNA Biomarkers.

Chronic venous disease (CVD) is a prevalent condition in adults, significantly affecting the global elderly population, with a higher incidence in women than in men. The modulation of gene expression through microRNA (miRNA) partly regulated the development of cardiovascular disease (CVD). Previous research identified a functional analysis of seven genes (CDS2, HDAC5, PPP6R2, PRRC2B, TBC1D22A, WNK1, and PABPC3) as targets of miRNAs related to CVD. In this context, miRNAs emerge as essential candidates for CVD diagnosis, representing novel molecular and biological knowledge. This work aims to identify, by network analysis, the miRNAs involved in CVD as potential biomarkers, either by interacting with small molecules such as toxins and pollutants or by searching for new drugs. Our study shows an updated landscape of the signaling pathways involving miRNAs in CVD pathology. This latest research includes data found through experimental tests and uses predictions to propose both miRNAs and genes as potential biomarkers to develop diagnostic and therapeutic methods for the early detection of CVD in the clinical setting. In addition, our pharmacological network analysis has, for the first time, shown how to use these potential biomarkers to find small molecules that may regulate them. Between the small molecules in this research, toxins, pollutants, and drugs showed outstanding interactions with these miRNAs. One of them, hesperidin, a widely prescribed drug for treating CVD and modulating the gene expression associated with CVD, was used as a reference for searching for new molecules that may interact with miRNAs involved in CVD. Among the drugs that exhibit the same miRNA expression profile as hesperidin, potential candidates include desoximetasone, curcumin, flurandrenolide, trifluridine, fludrocortisone, diflorasone, gemcitabine, floxuridine, and reversine. Further investigation of these drugs is essential to improve the treatment of cardiovascular disease. Additionally, supporting the clinical use of miRNAs as biomarkers for diagnosing and predicting CVD is crucial.

MicroRNA‑mediated approaches in ovarian cancer therapy: A comprehensive systematic review.

Ovarian cancer (OC) poses a significant health risk to women worldwide, with late diagnoses and chemotherapy resistance leading to high mortality rates. Despite several histological subtypes, the primary challenge remains the subtle nature of its symptoms, resulting in advanced-stage diagnosis and reduced treatment success rates. With platinum-based therapies showing relative efficacy but limited survival enhancements, the emergence of chemotherapy resistance during recurrence remains a critical obstacle. Precision medicine development has aimed to address these challenges in the context of the molecular diversity of OC. The present review explored the landscape of microRNA (miRNA)-mediated approaches in OC treatment. miRNAs have emerged as regulators of gene expression, serving as both oncogenes and tumor suppressors in OC. Dysregulated miRNAs are associated with disease progression and chemotherapy resistance, underscoring their significance in diagnosis and tailored treatment strategies. The present review extracted 295 publications from the PUBMED database. Out of the 73 eligible studies, 55 miRNAs were assessed. A total of three of these miRNAs were not associated with any disease or cancer, whilst eight were associated with OC, albeit also associated with other diseases. The present review encompassed three dimensions: i) The role of miRNAs in treatment efficacy; ii) the use of miRNAs to enhance therapy outcomes; and iii) adjunctive strategies for improved treatment results. Furthermore, it offered insights into potential avenues for improving OC treatment using miRNA-based approaches.

The Untapped Biomarker Potential of MicroRNAs for Health Risk-Benefit Analysis of Vaping vs. Smoking.

Despite the popularity of electronic cigarettes (e-cigs) among adolescent never-smokers and adult smokers seeking a less pernicious substitute for tobacco cigarettes, the long-term health impact of vaping is largely unknown. Like cigarette smoke, e-cig vapor contains harmful and potentially harmful compounds, although in fewer numbers and at substantially lower concentrations. Many of the same constituents of e-cig vapor and cigarette smoke induce epigenetic changes that can lead to the dysregulation of disease-related genes. MicroRNAs (MiRNAs) are key regulators of gene expression in health and disease states. Extensive research has shown that miRNAs play a prominent role in the regulation of genes involved in the pathogenesis of smoking-related diseases. However, the use of miRNAs for investigating the disease-causing potential of vaping has not been fully explored. This review article provides an overview of e-cigs as a highly consequential electronic nicotine delivery system, describes trends in e-cig use among adolescents and adults, and discusses the ongoing debate on the public health impact of vaping. Highlighting the significance of miRNAs in cell biology and disease, it summarizes the published and ongoing research on miRNAs in relation to gene regulation and disease pathogenesis in e-cig users and in vitro experimental settings. It identifies gaps in knowledge and priorities for future research while underscoring the need for empirical evidence that can inform the regulation of tobacco products to protect youth and promote public health.

Periodontal Tissue Homoeostasis, Immunity, the Red Complex Pathogens, and Dysbiosis: Unraveling the microRNA Effect.

microRNAs are a family of small, non-coding RNA molecules that can regulate the translation of messenger RNAs (mRNAs). Numerous miRNAs have been proposed as potential indicators for periodontal disease, and their regulation might serve as a potent means of restricting the disease process. MiRNAs act as important immune system regulators that promote the production of many cytokines, including interferon (IFN), tumour necrosis factor (TNF), and IL-1as well as RANK. Investigations pertaining to the use of specific miRNAs as therapeutic agents are underway. They can influence a variety of regulatory organs and target several genes. Additionally, distinct components of the same expression pathway can be controlled by combining miRNAs and their antagonists. In recent years, many miRNA delivery methods have been created for therapeutic applications. Studies pertaining to the role of miRNAs in periodontal disease pathogenesis may pave the way for the use of miRNAs as biomarkers of periodontal disease. A complete understanding of the role of miRNA in periodontal disease and its mechanism of action can pave the way towards therapeutic strategies that can reduce or even prevent the progression of periodontal diseases.

MiRNA Expression Profiling in G1 and G2 Pancreatic Neuroendocrine Tumors.

Pancreatic neuroendocrine neoplasms pose a growing clinical challenge due to their rising incidence and variable prognosis. The current study aims to investigate microRNAs (miRNA; miR) as potential biomarkers for distinguishing between grade 1 (G1) and grade 2 (G2) pancreatic neuroendocrine tumors (PanNET). A total of 33 formalin-fixed, paraffin-embedded samples were analyzed, comprising 17 G1 and 16 G2 tumors. Initially, literature-based miRNAs were validated via real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR), confirming significant downregulation of miR-130b-3p and miR-106b in G2 samples. Through next-generation sequencing, we have identified and selected the top six miRNAs showing the highest difference between G1 and G2 tumors, which were further validated. RT-qPCR validation confirmed the downregulation of miR-30d-5p in G2 tumors. miRNA combinations were created to distinguish between the two PanNET grades. The highest diagnostic performance in distinguishing between G1 and G2 PanNETs by a machine learning algorithm was achieved when using the combination miR-106b + miR-130b-3p + miR-127-3p + miR-129-5p + miR-30d-5p. The ROC analysis resulted in a sensitivity of 83.33% and a specificity of 87.5%. The findings underscore the potential use of miRNAs as biomarkers for stratifying PanNET grades, though further research is warranted to enhance diagnostic accuracy and clinical utility.

Insight into the Role of the miR-584 Family in Human Cancers.

Among the non-coding RNAs, the aberrant expression of microRNAs (miRNAs) is well described in the oncology field. It is clear that the altered expression of miRNAs is crucial for a variety of processes such as proliferation, apoptosis, motility, angiogenesis and metastasis insurgence. Considering these aspects, RNA-based therapies and the use of miRNAs as non-invasive biomarkers for early diagnosis are underlined as promising opportunities against cancer death. In the era of precision medicine, significant progress in next-generation sequencing (NGS) techniques has broadened knowledge regarding the miRNAs expression profile in cancer tissues and in the blood of cancer patients. In this scenario, pre-clinical and clinical studies suggested that the members of the miR-584 family, i.e., miR-584-5p and -3p, are prominent players in cancer development and progression. Under some conditions, these miRNAs are under-expressed in cancer tissues acting as tumor suppressors, while in other conditions, they are overexpressed, acting as oncogenes increasing the aggressive behavior of cancer cells. The aim of this review is to provide a comprehensive and up-to-date overview on the expression, upstream genes, molecular targets and signaling pathways influenced by the miR-584 family (i.e., miR-584-3p and -5p) in various human solid and hematological cancers. To achieve this goal, 64 articles on this topic are discussed. Among these articles, 55 are focused on miR-584-5p, and it is outlined how this miRNA could be used in future applications as a potential new therapeutic strategy and diagnostic tool.

Genetic Alchemy unveiled: MicroRNA-mediated gene therapy as the Artisan craft in the battlefront against hepatocellular carcinoma-a comprehensive chronicle of strategies and innovations.

Investigating therapeutic miRNAs is a rewarding endeavour for pharmaceutical companies. Since its discovery in 1993, our understanding of miRNA biology has advanced significantly. Numerous studies have emphasised the disruption of miRNA expression in various diseases, making them appealing candidates for innovative therapeutic approaches. Hepatocellular carcinoma (HCC) is a significant malignancy that poses a severe threat to human health, accounting for approximately 70%-85% of all malignant tumours. Currently, the efficacy of several HCC therapies is limited. Alterations in various biomacromolecules during HCC progression and their underlying mechanisms provide a basis for the investigation of novel and effective therapeutic approaches. MicroRNAs, also known as miRNAs, have been identified in the last 20years and significantly impact gene expression and protein translation. This atypical expression pattern is strongly associated with the onset and progression of various malignancies. Gene therapy, a novel form of biological therapy, is a prominent research area. Therefore, miRNAs have been used in the investigation of tumour gene therapy. This review examines the mechanisms of action of miRNAs, explores the correlation between miRNAs and HCC, and investigates the use of miRNAs in HCC gene therapy.

Changes in Circulating MicroRNA Levels as Potential Indicators of Training Adaptation in Professional Volleyball Players.

The increasing demand placed on professional athletes to enhance their fitness and performance has prompted the search for new, more sensitive biomarkers of physiological ability. One such potential biomarker includes microRNA (miRNA) small regulatory RNA sequences. The study investigated the levels of the selected circulating miRNAs before and after a 10-week training cycle in 12 professional female volleyball players, as well as their association with cortisol, creatine kinase (CK), and interleukin 6 (IL-6), using the qPCR technique. Significant decreases in the miR-22 (0.40 ± 0.1 vs. 0.28 ± 0.12, p = 0.009), miR-17 (0.35 ± 0.13 vs. 0.23 ± 0.08; p = 0.039), miR-24 (0.09 ± 0.04 vs. 0.05 ± 0.02; p = 0.001), and miR-26a (0.11 ± 0.06 vs. 0.06 ± 0.04; p = 0.003) levels were observed after training, alongside reduced levels of cortisol and IL-6. The correlation analysis revealed associations between the miRNAs' relative quantity and the CK concentrations, highlighting their potential role in the muscle repair processes. The linear regression analysis indicated that miR-24 and miR-26a had the greatest impact on the CK levels. The study provides insights into the dynamic changes in the miRNA levels during training, suggesting their potential as biomarkers for monitoring the adaptive responses to exercise. Overall, the findings contribute to a better understanding of the physiological effects of exercise and the potential use of miRNAs, especially miR-24 and miR-26a, as biomarkers in sports science and medicine.

Molecular Mechanisms in the Design of Novel Targeted Therapies for Neurodegenerative Diseases.

Neurodegenerative diseases are a diverse group of diseases characterized by a progressive loss of neurological function due to damage to nerve cells in the central nervous system. In recent years, there has been a worldwide increase in the expanding associated with increasing human life expectancy. Molecular mechanisms control many of the essential life processes of cells, such as replication, transcription, translation, protein synthesis and gene regulation. These are complex interactions that form the basis for understanding numerous processes in the organism and developing new diagnostic and therapeutic approaches. In the context of neurodegenerative diseases, molecular basis refers to changes at the molecular level that cause damage to or degeneration of nerve cells. These may include protein aggregates leading to pathological structures in brain cells, impaired protein transport in nerve cells, mitochondrial dysfunction, inflammatory processes or genetic mutations that impair nerve cell function. New medical therapies are based on these mechanisms and include gene therapies, reduction in inflammation and oxidative stress, and the use of miRNAs and regenerative medicine. The aim of this study was to bring together the current state of knowledge regarding selected neurodegenerative diseases, presenting the underlying molecular mechanisms involved, which could be potential targets for new forms of treatment.

Liquid biopsy utilizing miRNA in patients with advanced breast cancer treated with cyclin‑dependent kinase 4/6 inhibitors.

Cyclin-dependent kinase 4/6 inhibitors (CDK4/6is) are the mainstay of treatment of hormone receptor+/human epidermal growth factor receptor 2-patients with advanced breast cancer (ABC). Despite improvements in overall survival, most patients experience disease progression. Biomarkers derived from a liquid biopsy are appealing for their potential to detect resistance to treatment earlier than computed tomography imaging. However, clinical data concerning microRNAs (miRNAs/miRs) in the context of CDK4/6is are lacking. Thus, the present study assessed the use of miRNAs in patients with ABC treated with CDK4/6is. Patients treated for ABC with CDK4/6is between June and August 2022 were eligible. miRNA expression analyses were performed using a TaqMan™ low-density miRNA array. A total of 80 consecutive patients with ABC treated with CDK4/6is at Maria Sklodowska-Curie National Research Institute of Oncology (Gliwice, Poland) were assessed, with 14 patients diagnosed with progressive disease at the time of sampling, 55 patients exhibited clinical benefit from CDK4/6i treatment and 11 patients were at the beginning of CDK4/6i treatment. Patients with disease progression had significantly higher levels of miR-21 (P=0.027), miR-34a (P=0.011), miR-193b (P=0.032), miR-200a (P=0.027) and miR-200b (P=0.003) compared with patients who benefitted from CDK4/6i treatment. Significantly higher levels of miR-34a expression were observed in patients with progressive disease than in patients beginning treatment (P=0.031). The present study demonstrated the potential innovative role of circulating miRNAs during CDK4/6i treatment. Plasma-based expression of miR-21, -34a, -193b, -200a and -200b effectively distinguished patients with ABC who responded to CDK4/6i treatment from patients who were resistant. However, longitudinal studies are required to verify the predictive and prognostic potential of miRNA.

Development and validation of a clinical decision support system based on PSA, microRNAs, and MRI for the detection of prostate cancer

ObjectivesThe aims of this study are to develop and validate a clinical decision support system based on demographics, prostate-specific antigen (PSA), microRNA (miRNA), and MRI for the detection of prostate cancer (PCa) and clinical significant (cs) PCa, and to assess if this system performs better compared to MRI alone.MethodsThis retrospective, multicenter, observational study included 222 patients (mean age 66, range 46-75 years) who underwent prostate MRI, miRNA (let-7a-5p and miR-103a-3p) assessment, and biopsy. Monoparametric and multiparametric models including age, PSA, miRNA, and MRI outcome were trained on 65% of the data and then validated on the remaining 35% to predict both PCa (any Gleason grade [GG]) and csPCa (GG ≥ 2 vs GG = 1/negative). Accuracy, sensitivity, specificity, positive and negative predictive value (NPV), and area under the receiver operating characteristic curve were calculated.ResultsMRI outcome was the best predictor in the monoparametric model for both detection of PCa, with sensitivity of 90% (95%CI 73–98%) and NPV of 93% (95%CI 82–98%), and for csPCa identification, with sensitivity of 91% (95%CI 72–99%) and NPV of 95% (95%CI 84–99%). Sensitivity and NPV of PSA + miRNA for the detection of csPCa were not statistically different from the other models including MRI alone.ConclusionMRI stand-alone yielded the best prediction models for both PCa and csPCa detection in biopsy-naïve patients. The use of miRNAs let-7a-5p and miR-103a-3p did not improve classification performances compared to MRI stand-alone results.Clinical relevance statementThe use of miRNA (let-7a-5p and miR-103a-3p), PSA, and MRI in a clinical decision support system (CDSS) does not improve MRI stand-alone performance in the detection of PCa and csPCa.Key Points• Clinical decision support systems including MRI improve the detection of both prostate cancer and clinically significant prostate cancer with respect to PSA test and/or microRNA.• The use of miRNAs let-7a-5p and miR-103a-3p did not significantly improve MRI stand-alone performance.• Results of this study were in line with previous works on MRI and microRNA.

MICRORNAS AND THEIR RELEVANCE IN BONE REGENERATION AND DISEASE

Bone tissue is known to possess an intrinsic regeneration potential. However, in cases of major injury, trauma, and disease, bone loss is present, and the regeneration potential of the tissue is often impaired. The process of bone regeneration relies on a complex interaction of molecules. MicroRNAs (miRNA) are small, non-coding RNAs that inhibit messenger RNAs (mRNA). One miRNA can inhibit several mRNAs and one mRNA can be inhibited by several miRNAs. Functionally, miRNAs regulate the entire proteome via the local inhibition of translation. In fact, miRNA modulation has been shown to be involved in several musculoskeletal diseases1. In those pathologies, they modulate the transcriptional activity of mRNAs important for differentiation, tissue-specific activity, extracellular matrix production, etc. Because of their function in inhibiting translation, miRNAs are being researched in many diseases and are already being used for interventional treatment2. Bone tissue and its related conditions have been widely investigated up to this day1,3. This talk will focus on the relevancy of miRNAs to bone tissue, its homeostasis, and disease. After, examples will be given of how miRNAs can be used in bone regeneration and diseases such as osteoporosis and osteosarcoma. The use of miRNAs in both, detection and therapy will be discussed.

KLINICZNA ROLA BIOMARKERÓW miRNA W RAKU PŁASKONABŁONKOWYM KRTANI (LSCC). PRZEGLĄD LITERATURY

IntroductionMalignant transformations may result from gene dysregulation caused by genetic and epigenetic modifications. The use of miRNAs to treat cancer depends on the downregulation or upregulation of the miRNAs responsible for carcinogenesis (proliferation, angiogenesis, invasion, metastasis), providing the opportunity to suppress tumors. The purpose of this review is to list miRNAs identified so far as biomarkers in laryngeal squamous cell carcinoma (LSCC). This listing may help in predicting the evolution of miRNAs and developing anti-miRNAs and miRNA-mimics as anti-cancer therapies.Material and methodsRelevant publications from 2008 to 2022 were retrieved from the PubMed and Google Scholar databases, using the key words miRNA (PubMed – 149,294 results; Google Scholar – 205,000 results), laryngeal squamous cell carcinoma (PubMed – 33,191 results; Google Scholar – 17,900 results), laryngeal squamous cell carcinoma biomarkers (PubMed – 6249 results; Google Scholar – 18,000 results), laryngeal squamous cell carcinoma miRNA (PubMed – 1338 results; Google Scholar – 17,500 results). Eventually 51 papers were selected for review.ResultsWe identified 51 studies which have detected miRNA-based biomarkers for LSCC, and they are broadly reviewed here.ConclusionsThe identified laryngeal squamous cell-specific miRNA biomarkers appear to be promising for the detection, predicted course, and treatment of LSCC.

A Glimmer of Hope for Patients with a T3 Transformation Zone: miRNAs Are Potential Biomarkers for Cervical Dysplasia.

This pilot study assesses the potential use of miRNAs in the triage of colposcopy patients with type 3 (nonvisible) cervical transformation zone (TZ). Type 3 TZ is a constitutional finding associated with many problems and controversies in colposcopy patient management. Here, we present miRNAs as a potential biomarker for the detection of CIN3 in these cases. Cervical mucosa samples (CMS) were collected from patients presenting with T3 transformation zone during routine workup using the Cytobrush. Depending on the histological and cytological result, as well as the result of the routinely performed HPV PCR, patients were divided into three groups: patients with a high-grade intraepithelial lesion (CIN3) and a positive high-risk HPV test (CIN3 group), patients without an intraepithelial lesion and a positive high-risk HPV test (HPV group), and healthy controls (N = no intraepithelial lesion and negative HPV test). The cervical mucus samples included in the study were tested for their expression levels of distinct miRNAs using qPCR. All investigated miRNAs were consistently detectable in every sample. The CMSs of histologically graded CIN 3 showed consistently high expression levels of all eight miRNAs, whereas the CMSs from healthy patients (N) show generally lower expression levels. However, CMSs from patients of the HPV group represented a very heterogeneous group. The data presented here can provide a solid basis for future research into a triage test for patients with a T3 transformation zone on the basis of commonly used clinical equipment.

PROTEIN RAS-LIKE PROTEINS FROM RAT BRAIN SEBAGAI TARGET PENGHAMBATAN PERKEMBANGAN SEL KANKER

Ras-like proteins from rat brain (Rab) is one of the crucial proteins in the process of intracellular transport. Rab plays a role in delivering vesicles from the donor membrane to the acceptor membrane. Vesicles contain various molecules that are important in cell growth and development. These molecules are generally involved in some signaling pathways. In carrying out its functions, Rab needs to be activated first. The activation process of Rab involves various proteins. Thus, Rab activation and deactivation control are critical to regulating the movement of the transferred molecules. In cancer, there is an uncontrolled activation and deactivation of Rab. Rab's involvement in various signaling pathways by providing molecules needed for growth and development is a basis for increasing the speed of growth and development of cancer cells. Although Rab is not the main factor causing cancer, it can help the development of cancer. So, it can be one of the keys to controlling the transfer of molecules involved in the growth and development of cancer cells. There are several methods related to the activation of Rab for molecular transport. Rab activation inhibition by Rab inhibitors and inhibitors of Rab activating proteins and the use of miRNAs can prevent molecule transport. Thus, control of Rab activation can be an alternative to suppress the growth and development of cancer cells.

Circulating miRNA-122 is associated with knee osteoarthritis progression: A 6-year longitudinal cohort study in the Yakumo study

ObjectiveThe association between knee osteoarthritis (OA) and miRNAs has been widely reported. However, the utility of miRNAs as predictors of knee osteoarthritis (KOA) progression in longitudinal studies has not been reported. We aimed to identify circulating miRNAs (c-miRNAs) associated with KOA progression in the general population and to examine their potential use as predictors of KOA progression. MethodsIn 2012 and 2018, 66 participants (128 knees) took part in a resident health check-up in the Yakumo study. If the KL classification progressed two or more levels, the patient was classified as having progressive OA. Quantitative real-time polymerase chain reaction was used to screen 21 c-miRNAs. The expression levels of those c-miRNAs were compared between the progressive OA group and non-progressive OA group using student-t-test. Logistic analysis was performed in c-miRNAs less than p < 0.10 in univariate analysis. ResultsThe progressive OA group consisted of 78 knees. The results of the comparison between the progressive OA group and the non-progressive OA group showed that six c-miRNAs as follows; let7d (p = 0.030), c-miRNA-122 (p < 0.001), 150 (p = 0.070), 199 (p = 0.078), 21 (p = 0.016) and 320 (p = 0.093) were extracted as factors related to the progression of knee OA. In addition, logistic regression analysis identified c-miRNA-122 as an independent factor involved in the progression of knee osteoarthritis (odds ratio: 1.510, 95% confidence interval: 1.060–2.140, p = 0.023). The ROC curve showed by c-miRNA-122 for the progression of OA risk had an area under the curve of 0.702 (95% CI: 0.609–0.795). The threshold of c-miRNA-122 was −4.609. ConclusionThe expression level of c-miRNA-122 was associated with the risk of KOA progression in community dwelling Japanese people.

Exosomal microRNA/miRNA Dysregulation in Respiratory Diseases: From Mycoplasma-Induced Respiratory Disease to COVID-19 and Beyond.

Respiratory diseases represent a significant economic and health burden worldwide, affecting millions of individuals each year in both human and animal populations. MicroRNAs (miRNAs) play crucial roles in gene expression regulation and are involved in various physiological and pathological processes. Exosomal miRNAs and cellular miRNAs have been identified as key regulators of several immune respiratory diseases, such as chronic respiratory diseases (CRD) caused by Mycoplasma gallisepticum (MG), Mycoplasma pneumoniae pneumonia (MMP) caused by the bacterium Mycoplasma pneumoniae, coronavirus disease 2019 (COVID-19), chronic obstructive pulmonary disease (COPD), asthma, and acute lung injury/acute respiratory distress syndrome (ALI/ARDS). Consequently, miRNAs seem to have the potential to serve as diagnostic biomarkers and therapeutic targets in respiratory diseases. In this review, we summarize the current understanding of the functional roles of miRNAs in the above several respiratory diseases and discuss the potential use of miRNAs as stable diagnostic biomarkers and therapeutic targets for several immune respiratory diseases, focusing on the identification of differentially expressed miRNAs and their targeting of various signaling pathways implicated in disease pathogenesis. Despite the progress made, unanswered questions and future research directions are discussed to facilitate personalized and targeted therapies for patients with these debilitating conditions.

MicroRNA Profile, Putative Diagnostic Biomarkers and RNA-Based Therapies in the Inherited Lipid Storage Disease Niemann-Pick Type C.

Lipids are essential for cellular function and are tightly controlled at the transcriptional and post-transcriptional levels. Dysregulation of these pathways is associated with vascular diseases, diabetes, cancer, and several inherited metabolic disorders. MicroRNAs (miRNAs), in particular, are a family of post-transcriptional gene repressors associated with the regulation of many genes that encode proteins involved in multiple lipid metabolism pathways, thereby influencing their homeostasis. Thus, this class of non-coding RNAs (ncRNAs) has emerged as a promising therapeutic target for the treatment of lipid-related metabolic alterations. Most of these miRNAs act at an intracellular level, but in the past few years, a role for miRNAs as intercellular signaling molecules has also been uncovered since they can be transported in bodily fluids and used as potential biomarkers of lipid metabolic alterations. In this review, we point out the current knowledge on the miRNA signature in a lysosomal storage disorder associated with lipid dysfunction, Niemann-Pick type C, and discuss the potential use of miRNAs as biomarkers and therapeutic targets for RNA-based therapies.

The Roles of microRNAs in the Cardiovascular System.

The discovery of miRNAs and their role in disease represent a significant breakthrough that has stimulated and propelled research on miRNAs as targets for diagnosis and therapy. Cardiovascular disease is an area where the restrictions of early diagnosis and conventional pharmacotherapy are evident and deserve attention. Therefore, miRNA-based drugs have significant potential for development. Research and its application can make considerable progress, as seen in preclinical and clinical trials. The use of miRNAs is still experimental but has a promising role in diagnosing and predicting a variety of acute coronary syndrome presentations. Its use, either alone or in combination with currently available biomarkers, might be adopted soon, particularly if there is diagnostic ambiguity. In this review, we examine the current understanding of miRNAs as possible targets for diagnosis and treatment in the cardiovascular system. We report on recent advances in recognising and characterising miRNAs with a focus on clinical translation. The latest challenges and perspectives towards clinical application are discussed.

MicroRNA based combinatorial therapy against TKIs resistant CML by inactivating the PI3K/Akt/mTOR pathway: a review.

Chronic myeloid leukemia (CML) is characterized by presence of Philadelphia chromosome, which harbors BCR-ABL oncogene responsible for encoding BCR-ABL oncoprotein. This oncoprotein interferes with cellular signaling pathways, resulting in tumor progression. Among these pathways, PI3K/Akt/mTOR pathway is significantly upregulated in CML. Tyrosine kinase inhibitors (TKIs) are current standard therapy for CML, and they have shown remarkable efficacy. However, emergence of TKIs drug resistance has necessitated investigation of novel therapeutic approaches. Components of PI3K/Akt/mTOR pathway have emerged as attractive targets in this context, as this pathway is known to be activated in TKIs-resistant CML cells/patients. Inhibiting this pathway may provide a complementary approach to improving TKIs' efficacy and treatment outcomes. Given previous research indicating that miRNAs play an inhibitory role in cancer, current study used computational tools to identify miRNAs that specifically target pathway's core components. A comprehensive analysis was performed, resulting in identification of 111 miRNAs that potentially target PI3K/Akt/mTOR pathway. From this extensive list, 7 miRNAs was selected for further investigation based on their consistent downregulation across leukemia subtypes. Except for hsa-miR-199a-3p, remaining six miRNAs have been extensively studied in acute myeloid leukemia (AML). Given high similarity between AML and CML, it is believed that six miRNAs which are not studied in context of CML may also be advantageous for curing chemoresistance in CML. Building upon this knowledge, it is reasonable to speculate that a combination therapy approach involving use of miRNAs alongside TKIs may offer improved therapy for TKIs-resistant CML compared to TKIs monotherapy alone.