scholarly journals Therapeutic Approaches and Role of ncRNAs in Cardiovascular Disorders and Insulin Resistance

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Kalupahana Irushi Pamodya Liyanage ◽  
Gamage Upeksha Ganegoda
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Cardiovascular Diseases ◽  
Gene Expression Regulation ◽  
Therapeutic Approaches ◽  
Gene Expressions ◽  
Diagnostic Biomarkers ◽  
Cellular Processes ◽  
Regulatory Functions

Diseases resulting from alterations in gene expressions through mutations in the genes or through changes in the gene expression regulation could be identified through the analysis of RNA expressions. ncRNAs play a significant role in regulation of the gene expression by controlling the expression levels of the coding RNAs and other cellular processes. Discoveries have shown that the human genome is encoded with sequences responsible for the transcription of thousands of ncRNAs. Even though the studies conducted on ncRNAs are still at initial stages, facts established so far display biomarkers that confirm their relationship with certain diseases such as cancers, cardiovascular diseases, and insulin resistance. These studies have been facilitated with high throughput modern sequencing techniques such as microarrays and RNA sequencing. The data obtained through the above analysis are processed with the aid of existing databases, to deduce conclusions on different diagnostic biomarkers and therapeutic targets for specific diseases. This review focuses on the association of ncRNAs in disease prediction, focusing mainly on cardiovascular diseases and disorders caused by insulin resistance. The report also analyzes regulatory functions of ncRNAs and novel approaches used in disease therapeutics.

scholarly journals Prediction of probable impact of miR-34a and miR-215 on differentiation of naive CD4+ T cells to Th17 cells in multiple sclerosis

2018 ◽  
Vol 21 (6) ◽  
pp. 276-279
Author(s):  
Nooshin Ghadiri ◽  
Aref Hoseini ◽  
Kamran Ghaedi ◽  
Negar Alsadat Emamnia ◽  
Mazdak Ganjalikhani-Hakemi ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Th17 Cells ◽  
Therapeutic Approaches ◽  
Diagnostic Biomarkers ◽  
Cellular Processes ◽  
High Prevalence ◽  
Probable Impact ◽  
Non Coding Rnas ◽  
Th17 Differentiation

Background and aims: miRNAs, as a class of non-coding RNAs, take part in different cellular processes. Dysregulation of different miRNAs has been reported in numerous disorders to date. Multiple sclerosis (MS) is an autoimmune disease with high prevalence in Iran and Th17 cells play an important role in its pathogenesis. In the current study, we aimed to predict the possible role of miR-34a and miR-215 in the process of controlling Th17 differentiation, and hence, their possible impact on the onset and progression of MS. Methods: We investigated probable interactions of miRNAs and genes that participate in Th17 cells differentiation using miRwalk database as an integrative one which utilizes 10 different algorithms to predict miRNA-mRNA interaction. Results: Based on our findings, miR-34a and miR-215 were predicted to have a potential role in the induction of Th17 cells differentiation. Conclusion: Conclusively, miR-34a and miR-215 may up-regulate Th17 cells of MS patients. Since bioinformatics data have shown that these miRNAs suppress negative regulatory genes in Th17 cells differentiation, we suppose that down-regulation of these miRNAs could ameliorate MS symptoms. Therefore, several therapeutic approaches may be considered for these miRNAs besides their application as valuable prognostic/diagnostic biomarkers in detection of various stages of MS.

MiRNA-145 and Its Direct Downstream Targets in Digestive System Cancers: A Promising Therapeutic Target

2020 ◽  
Vol 26 ◽  
Author(s):  
Yini Ma ◽  
Xiu Cao ◽  
Guojuan Shi ◽  
Tianlu Shi
Keyword(s):  
Digestive System ◽  
Target Genes ◽  
Malignant Neoplasm ◽  
Vital Role ◽  
Diagnostic Biomarkers ◽  
Cellular Processes ◽  
Promising Therapeutic Target ◽  
Direct Target ◽  
Potential Strategy

: MicroRNAs (miRNAs) play a vital role in the onset and development of many diseases, including cancers. Emerging evidence shows that numerous miRNAs have the potential to be used as diagnostic biomarkers for cancers, and miRNA-based therapy may be a promising therapy for the treatment of malignant neoplasm. MicroRNA-145 (miR-145) has been considered to play certain roles in various cellular processes, such as proliferation, differentiation and apoptosis, via modulating expression of direct target genes. Recent reports show that miR-145 participates in the progression of digestive system cancers, and plays crucial and novel roles for cancer treatment. In this review, we summarize the recent knowledge concerning the function of miR-145 and its direct targets in digestive system cancers. We discuss the potential role of miR-145 as valuable biomarkers for digestive system cancers and how miR-145 regulates these digestive system cancers via different targets to explore the potential strategy of targeting miR-145.

scholarly journals A UPF1 variant drives conditional remodeling of nonsense-mediated mRNA decay

2021 ◽  
Author(s):  
Sarah E. Fritz ◽  
Soumya Ranganathan ◽  
J. Robert Hogg
Keyword(s):  
Gene Expression ◽  
Mrna Decay ◽  
Gene Expression Regulation ◽  
Translation Termination ◽  
Translational Repression ◽  
The Core ◽  
Human Genes ◽  
Rna Quality Control ◽  
Nonsense Mediated Mrna Decay

AbstractThe nonsense-mediated mRNA decay (NMD) pathway monitors translation termination to degrade transcripts with premature stop codons and regulate thousands of human genes. Due to the major role of NMD in RNA quality control and gene expression regulation, it is important to understand how the pathway responds to changing cellular conditions. Here we show that an alternative mammalian-specific isoform of the core NMD factor UPF1, termed UPF1LL, enables condition-dependent remodeling of NMD specificity. UPF1LL associates more stably with potential NMD target mRNAs than the major UPF1SL isoform, expanding the scope of NMD to include many transcripts normally immune to the pathway. Unexpectedly, the enhanced persistence of UPF1LL on mRNAs supports induction of NMD in response to rare translation termination events. Thus, while canonical NMD is abolished by translational repression, UPF1LL activity is enhanced, providing a mechanism to rapidly rewire NMD specificity in response to cellular stress.

scholarly journals Evaluation of potential gene expression as early markers of insulin resistance and non-alcoholic fatty liver disease in the Indonesian population

2018 ◽  
Vol 23 (2) ◽  
pp. 84
Author(s):  
Eunice Limantara ◽  
Felicia Kartawidjajaputra ◽  
Antonius Suwanto
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Model Assessment ◽  
Gene Expressions ◽  
Alcoholic Fatty Liver ◽  
Early Markers ◽  
Alcoholic Fatty Liver Disease

Early detection of insulin resistance (IR) or non-alcoholic fatty liver disease (NAFLD) is crucial to preventing future risks of developing chronic diseases. The Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), Liver Fat Score (LFS), and Fatty Liver Index (FLI) are generally employed to measure severity stages of IR and NAFLD. The study of gene expressions could explain the molecular mechanisms that occur early on in IR and NAFLD; thus providing potential early markers for both diseases. This study was conducted to evaluate the gene expressions that could potentially be early markers of IR and NAFLD. All participants (n = 21) had normal blood glucose and were categorized as without hepatosteatosis (n = 10), at higher risk of hepatosteatosis (n = 6), and hepatosteatosis (n = 5). Gene expression analysis was performed using the 2-∆∆CT relative quantification method. There were significant differences in galnt2 (p < 0.002) and sirt1 (p < 0.010) expression between the first and the third tertiles of HOMA-IR; and in ptpn1 (p < 0.012) expression between the first and the second tertiles of LFS. In conclusion, the expressions of galnt2 and sirt1 could be used as early markers of IR, while the expression of ptpn1 could be employed as an early marker of NAFLD.

scholarly journals The Role of N6-Methyladenosine (m6A) Methylation Modifications in Hematological Malignancies

Cancers ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 332
Author(s):  
Yan Zhao ◽  
Hongling Peng
Keyword(s):  
Bone Marrow ◽  
Pluripotent Stem Cells ◽  
Rna Splicing ◽  
Messenger Rna ◽  
Hematologic Malignancies ◽  
Cellular Processes ◽  
Proliferation And Differentiation ◽  
Regulatory Functions ◽  
Increased Susceptibility

Epigenetics is identified as the study of heritable modifications in gene expression and regulation that do not involve DNA sequence alterations, such as DNA methylation, histone modifications, etc. Importantly, N6-methyladenosine (m6A) methylation modification is one of the most common epigenetic modifications of eukaryotic messenger RNA (mRNA), which plays a key role in various cellular processes. It can not only mediate various RNA metabolic processes such as RNA splicing, translation, and decay under the catalytic regulation of related enzymes but can also affect the normal development of bone marrow hematopoiesis by regulating the self-renewal, proliferation, and differentiation of pluripotent stem cells in the hematopoietic microenvironment of bone marrow. In recent years, numerous studies have demonstrated that m6A methylation modifications play an important role in the development and progression of hematologic malignancies (e.g., leukemia, lymphoma, myelodysplastic syndromes [MDS], multiple myeloma [MM], etc.). Targeting the inhibition of m6A-associated factors can contribute to increased susceptibility of patients with hematologic malignancies to therapeutic agents. Therefore, this review elaborates on the biological characteristics and normal hematopoietic regulatory functions of m6A methylation modifications and their role in the pathogenesis of hematologic malignancies.

scholarly journals MicroRNA-143/-145 in Cardiovascular Diseases

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Wang Zhao ◽  
Shui-Ping Zhao ◽  
Yu-Hong Zhao
Keyword(s):  
Smooth Muscle ◽  
Cardiovascular Diseases ◽  
Vascular Smooth Muscle Cells ◽  
Essential Role ◽  
Recent Progress ◽  
Potential Role ◽  
Phenotypic Switching ◽  
Diagnostic Biomarkers ◽  
Potential Strategy

MicroRNAs (miRNAs) play an essential role in the onset and development of many cardiovascular diseases. Increasing evidence shows that miRNAs can be used as potential diagnostic biomarkers for cardiovascular diseases, and miRNA-based therapy may be a promising therapy for the treatment of cardiovascular diseases. The microRNA-143/-145 (miR-143/-145) cluster is essential for differentiation of vascular smooth muscle cells (VSMCs) and determines VSMC phenotypic switching. In this review, we summarize the recent progress in knowledge concerning the function of miR-143/-145 in the cardiovascular system and their role in cardiovascular diseases. We discuss the potential role of miR-143/-145 as valuable biomarkers for cardiovascular diseases and explore the potential strategy of targeting miR-143 and miR-145.

scholarly journals Adipocyte PU.1 knockout promotes insulin sensitivity in HFD-fed obese mice

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Denise E. Lackey ◽  
Felipe C. G. Reis ◽  
Roi Isaac ◽  
Rizaldy C. Zapata ◽  
Dalila El Ouarrat ◽  
...  
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Target Genes ◽  
Obese Mice ◽  
Tissue Macrophage

Abstract Insulin resistance is a key feature of obesity and type 2 diabetes. PU.1 is a master transcription factor predominantly expressed in macrophages but after HFD feeding PU.1 expression is also significantly increased in adipocytes. We generated adipocyte specific PU.1 knockout mice using adiponectin cre to investigate the role of PU.1 in adipocyte biology, insulin and glucose homeostasis. In HFD-fed obese mice systemic glucose tolerance and insulin sensitivity were improved in PU.1 AKO mice and clamp studies indicated improvements in both adipose and liver insulin sensitivity. At the level of adipose tissue, macrophage infiltration and inflammation was decreased and glucose uptake was increased in PU.1 AKO mice compared with controls. While PU.1 deletion in adipocytes did not affect the gene expression of PPARg itself, we observed increased expression of PPARg target genes in eWAT from HFD fed PU.1 AKO mice compared with controls. Furthermore, we observed decreased phosphorylation at serine 273 in PU.1 AKO mice compared with fl/fl controls, indicating that PPARg is more active when PU.1 expression is reduced in adipocytes. Therefore, in obesity the increased expression of PU.1 in adipocytes modifies the adipocyte PPARg cistrome resulting in impaired glucose tolerance and insulin sensitivity.

scholarly journals Insulin resistance in obese adolescents affects the expression of genes associated with immune response

2019 ◽  
Vol 53 (2) ◽  
pp. 71-82 ◽  
Author(s):  
Dmytro O. Minchenko
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Immune Response ◽  
Expression Level ◽  
Control Group ◽  
Gene Expressions ◽  
Down Regulation ◽  
Metabolic Complications ◽  
Obese Adolescents ◽  
Expression Of Genes

AbstractObjective. The development of obesity and its metabolic complications is associated with dysregulation of various intrinsic mechanisms, which control basic metabolic processes through changes in the expression of numerous regulatory genes.Methods. The expression level of HLA-DRA, HLA-DRB1, HLA-G, HLA-F, and NFX1 genes as well as miR-190b was measured in the blood of obese adolescents without signs of resistance to insulin and with insulin resistance in comparison with the group of relative healthy control individuals without signs of obesity.Results. It was shown that obesity without signs of insulin resistance is associated with upregulation of the expression level of HLA-DRA and HLA-DRB1 genes, but with down-regulation of HLA-G gene expression in the blood as compared to control group of relative healthy adolescents. At the same time, no significant changes were observed in the expression level of HLA-F and NFX1 genes in the blood of this group of obese adolescents. Development of insulin resistance in obese individuals leads to significant down-regulation of HLA-DRA, HLA-DRB1, HLA-G, and HLA-F gene expressions as well as to up-regulation of NFX1 gene as well as microRNA miR-190b in the blood as compared to obese patients without signs of insulin resistance.Conclusions. Results of this study provide evidence that obesity affects the expression of the subset of genes related to immune response in the blood and that development of insulin resistance in obese adolescents is associated with strong down-regulation of the expressions of HLA-DRA, HLA-DRB1, HLA-F, and HLA-G genes, which may be contribute to the development of obesity complications. It is possible that transcription factor NFX1 and miR-190b participate in downregulation of HLA-DRA gene expression in the blood of obese adolescents with insulin resistance.

scholarly journals Fatty acids, epigenetic mechanisms and chronic diseases: a systematic review

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
K. González-Becerra ◽  
O. Ramos-Lopez ◽  
E. Barrón-Cabrera ◽  
J. I. Riezu-Boj ◽  
F. I. Milagro ◽  
...  
Keyword(s):  
Gene Expression ◽  
Systematic Review ◽  
Fatty Acids ◽  
Chronic Diseases ◽  
Gene Expression Regulation ◽  
Saturated Fatty Acids ◽  
Dietary Fatty Acids ◽  
Epigenetic Mechanisms ◽  
Metabolic Alterations

Abstract Background Chronic illnesses like obesity, type 2 diabetes (T2D) and cardiovascular diseases, are worldwide major causes of morbidity and mortality. These pathological conditions involve interactions between environmental, genetic, and epigenetic factors. Recent advances in nutriepigenomics are contributing to clarify the role of some nutritional factors, including dietary fatty acids in gene expression regulation. This systematic review assesses currently available information concerning the role of the different fatty acids on epigenetic mechanisms that affect the development of chronic diseases or induce protective effects on metabolic alterations. Methods A targeted search was conducted in the PubMed/Medline databases using the keywords “fatty acids and epigenetic”. The data were analyzed according to the PRISMA-P guidelines. Results Consumption fatty acids like n-3 PUFA: EPA and DHA, and MUFA: oleic and palmitoleic acid was associated with an improvement of metabolic alterations. On the other hand, fatty acids that have been associated with the presence or development of obesity, T2D, pro-inflammatory profile, atherosclerosis and IR were n-6 PUFA, saturated fatty acids (stearic and palmitic), and trans fatty acids (elaidic), have been also linked with epigenetic changes. Conclusions Fatty acids can regulate gene expression by modifying epigenetic mechanisms and consequently result in positive or negative impacts on metabolic outcomes.

scholarly journals lncRNA and Mechanisms of Drug Resistance in Cancers of the Genitourinary System

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2148 ◽  
Author(s):  
Dominik A. Barth ◽  
Jaroslav Juracek ◽  
Ondrej Slaby ◽  
Martin Pichler ◽  
George A. Calin
Keyword(s):  
Drug Resistance ◽  
Treatment Options ◽  
Cancer Therapies ◽  
Protein Coding ◽  
Genitourinary System ◽  
Cellular Processes ◽  
Rna Transcripts ◽  
Novel Therapeutic Strategies ◽  
Regulatory Functions

Available systemic treatment options for cancers of the genitourinary system have experienced great progress in the last decade. However, a large proportion of patients eventually develop resistance to treatment, resulting in disease progression and shorter overall survival. Biomarkers indicating the increasing resistance to cancer therapies are yet to enter clinical routine. Long non-coding RNAs (lncRNA) are non-protein coding RNA transcripts longer than 200 nucleotides that exert multiple types of regulatory functions of all known cellular processes. Increasing evidence supports the role of lncRNAs in cancer development and progression. Additionally, their involvement in the development of drug resistance across various cancer entities, including genitourinary malignancies, are starting to be discovered. Consequently, lncRNAs have been suggested as factors in novel therapeutic strategies to overcome drug resistance in cancer. In this review, the existing evidences on lncRNAs and their involvement in mechanisms of drug resistance in cancers of the genitourinary system, including renal cell carcinoma, bladder cancer, prostate cancer, and testicular cancer, will be highlighted and discussed to facilitate and encourage further research in this field. We summarize a significant number of lncRNAs with proposed pathways in drug resistance and available reported studies.

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