scholarly journals Expression Profiles of Circulating microRNAs in South African Type 2 Diabetic Individuals on Treatment

2021 ◽  
Vol 12 ◽  
Author(s):  
Cecil J. Weale ◽  
Don M. Matshazi ◽  
Saarah F. G. Davids ◽  
Shanel Raghubeer ◽  
Rajiv T. Erasmus ◽  
...  
Keyword(s):  
South African ◽  
Insulin Signalling ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Response To Treatment ◽  
Blood Levels ◽  
Newly Diagnosed ◽  
Altered Expression ◽  
Diabetic Treatment

Aim: The influence of disease duration and anti-diabetic treatment on epigenetic processes has been described, with limited focus on interactions with microRNAs (miRNAs). miRNAs have been found to play key roles in the regulation of pathways associated with type 2 diabetes mellitus (T2DM), and expression patterns in response to treatment may further promote their use as therapeutic targets in T2DM and its associated complications. We therefore aimed to investigate the expressions of circulating miRNAs (miR-30a-5p, miR-1299, miR-182-5p, miR-30e-3p and miR-126-3p) in newly diagnosed and known diabetics on treatment, in South Africa.Methods: A total of 1254 participants with an average age of 53.8years were included in the study and classified according to glycaemic status (974 normotolerant, 92 screen-detected diabetes and 188 known diabetes). Whole blood levels of miR-30a-5p, miR-1299, miR-182-5p, miR-30e-3p and miR-126-3p were quantitated using RT-qPCR. Expression analysis was performed and compared across groups.Results: All miRNAs were significantly overexpressed in subjects with known diabetes when compared to normotolerant individuals, as well as known diabetics vs. screen-detected (p<0.001). Upon performing regression analysis, of all miRNAs, only miR-182-5p remained associated with the duration of the disease after adjustment for type of treatment (OR: 0.127, CI: 0.018–0.236, p=0.023).Conclusion: Our findings revealed important associations and altered expression patterns of miR-30a-5p, miR-1299, miR-182-5p, miR-30e-3p and miR-126-3p in known diabetics on anti-diabetic treatment compared to newly diagnosed individuals. Additionally, miR-182-5p expression decreased with increasing duration of T2DM. Further studies are, however, recommended to shed light on the involvement of the miRNA in insulin signalling and glucose homeostasis, to endorse its use as a therapeutic target in DM and its associated complications.

scholarly journals Nitric Oxide-Mediated Transcriptional Changes in Arabidopsis thaliana

2003 ◽  
Vol 16 (12) ◽  
pp. 1094-1105 ◽  
Author(s):  
Annalisa Polverari ◽  
Barbara Molesini ◽  
Mario Pezzotti ◽  
Roberto Buonaurio ◽  
Mario Marte ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Stress Response ◽  
Plant Resistance ◽  
Expression Profiles ◽  
Expression Patterns ◽  
No Production ◽  
Cellular Transport ◽  
Defense Gene Expression ◽  
Altered Expression ◽  
Transcriptional Changes

Nitric oxide (NO) is an essential regulatory molecule in several developmental processes and in the stress response in both animal and plant systems. Furthermore, key features of plant resistance to pathogens have been shown to depend on NO production, e.g., defense gene expression and the activation of a hypersensitive reaction (HR) in synergy with reactive oxygen species (ROS). Due to the many possible mechanisms of NO action, a clear picture of its involvement in plant resistance to pathogens is far from being achieved. Transcriptional changes related to NO action are likely to play a significant role in resistance and cell death. We investigated the changes in the expression profiles of Arabi-dopsis thaliana following infiltration with the NO donor sodium nitroprusside, by cDNA-amplification fragment length polymorphism (AFLP) transcript profiling. Altered expression patterns were detected for 120 of the approximately 2,500 cDNAs examined. Sequence analysis revealed homologies with genes involved in signal transduction, disease resistance and stress response, photosynthesis, cellular transport, and basic metabolism or with sequences coding for unknown proteins. Comparison of the expression profiles with data from public microarray sources revealed that many of the identified genes modulated by NO were previously reported to be modulated in disease-related experiments.

scholarly journals Application of the AMLprofiler Diagnostic Microarray in the South African Setting

2017 ◽  
Vol 2017 ◽  
pp. 1-8
Author(s):  
S. S. Kappala ◽  
M. Alessandrini ◽  
T. Matlhako ◽  
E. Beltchev ◽  
R. Pool ◽  
...  
Keyword(s):  
South Africa ◽  
Bone Marrow ◽  
South African ◽  
De Novo ◽  
Survival Rates ◽  
Gene Profiling ◽  
Response To Treatment ◽  
Altered Expression ◽  
De Novo Aml

Acute myeloid leukemia (AML) is characterized by proliferation of the myeloid lineage and accumulation of immature hematopoietic cells in the bone marrow and is typified by marked heterogeneity both in response to treatment and survival. AMLprofiler is a qualitative in vitro diagnostic microarray incorporating seven molecular biomarkers used to diagnose and predict posttherapy survival rates. In this study, we compared AMLprofiler to routine AML diagnostic methodologies employed in South Africa, focusing on consistency of the results, cost, and time to result. RNA was isolated from bone marrow and peripheral blood samples from patients with de novo AML and was processed using Affymetrix Gene Profiling Reagent kits. The results from AMLprofiler and standard methodologies were highly comparable. In addition, many samples were determined to be positive for biomarkers not routinely investigated in South Africa, namely, CEBPA double mutants, NPM1 variants, and altered expression levels of BAALC and EVI1. 38% of samples presented with no positive biomarker; AMLprofiler nonetheless enabled 26% of AML patients to be classified into either favorable or poor prognostic categories. This study highlights the comprehensive nature of the microarray. Decreased time to result and refinement of risk stratification are notable benefits.

scholarly journals MicroRNA profiling and their pathways in South African individuals with prediabetes and newly diagnosed type 2 diabetes mellitus

Oncotarget ◽  
2018 ◽  
Vol 9 (55) ◽  
pp. 30485-30498 ◽  
Author(s):  
Tandi E. Matsha ◽  
Andre P. Kengne ◽  
Stanton Hector ◽  
Desiree L. Mbu ◽  
Yandiswa Y. Yako ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
South African ◽  
Newly Diagnosed ◽  
Microrna Profiling

scholarly journals Downregulation of miR-24-3p and miR-198 in Newly Diagnosed type 2 Diabetes Mellitus

2021 ◽  
Author(s):  
Abhilasha Abhilasha ◽  
Prasenjit Mitra ◽  
Smriti Suri ◽  
Indu Saxena ◽  
Ravindra KG Shukla ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Internal Control ◽  
Insulin Signalling ◽  
Venous Blood ◽  
Fold Change ◽  
Newly Diagnosed ◽  
Expression Levels

Abstract Introduction: Type 2 Diabetes mellitus (T2DM) is a metabolic disorder related to genetic, lifestyle, and environmental factors. It is characterized by hyperglycaemia, primarily due to insulin resistance. Recent studies have shown that microRNAs have been involved in the regulation of post-transcriptional gene expression mainly by repressing protein production. Dysregulated miRNA in type 2 diabetes interrupts the insulin signalling cascade and multiple physiological processes leading to disease progression. miRNAs are released from cells in circulation and are now known as a new class of biomarkers due to their stable nature. miR-24-3p and miR-198 are associated with several diseases but their role in type 2 diabetes remains unclear. This study aimed to compare miR-24-3p and miR-198 expression levels in newly diagnosed Type 2 Diabetes Mellitus patients and Non-T2DM controls. Method: Thirty-five newly diagnosed type 2 diabetic cases and thirty-five Non-T2DM controls were recruited after obtaining due informed consent. Venous blood was obtained under aseptic conditions. Biochemical parameters were analyzed using the autoanalyzer. Expression levels of miR-24-3p and miR-198 were performed using RT-PCR by TaqMan Advanced miRNA assay. miR-16-5p was used as an internal control. Results: The difference between circulating levels of whole blood of miR-24-3p and miR-198 was statistically significant among the study group. miR-24-3p showed a fold change of 0.312 and miR-198 showed a fold change of 0.203. The miRNAs were not correlated with the glycaemic and other clinical parameters. Conclusions: Findings of our study suggests that expression of miR-24-3p and miR-198 are downregulated in newly diagnosed Type 2 Diabetes Mellitus.

scholarly journals Correlation between Expression Profiles of Key Signaling Genes in Colorectal Cancer Samples from Type 2 Diabetic and Non-Diabetic Patients

Life ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 216
Author(s):  
Zsuzsanna Elek ◽  
Zsolt Rónai ◽  
Gergely Keszler ◽  
László Harsányi ◽  
Endre Kontsek ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Internal Control ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Enrichment Analysis ◽  
Differentially Expressed ◽  
Diabetic Patients ◽  
Mrna Levels ◽  
Type 2 Diabetic

Several lines of epidemiological and biochemical evidence support the association of type 2 diabetes mellitus (T2DM) and colorectal cancer (CRC). T2DM has been shown to impinge on the transcriptome of colon tumor cells, promoting their proliferation and invasion. In order to gain insight into diabetes-specific modulation of colon cancer signaling, we analyzed gene expression patterns of more than five hundred genes encoding signaling proteins on TaqMan OpenArray panels from colonoscopic colorectal tumor samples of type 2 diabetic and non-diabetic patients. In total, 48 transcripts were found to be differentially expressed in tumors of T2DM patients as compared to healthy colon samples. Enrichment analysis with the g:GOSt (Gene Ontology Statistics) functional profiling tool revealed that the underlying genes can be classified into five signaling pathways (in decreasing order of significance: Wnt (wingless-type)/β-catenin; Hippo; TNF (tumor necrosis factor); PI3K/Akt (phosphoinositide-3 kinase/protein kinase B), and platelet activation), implying that targeted downregulation of these signaling cascades might help combat CRC in diabetic patients. Transcript levels of some of the differentially expressed genes were also measured from surgically removed diabetic and non-diabetic CRC specimens by individual qPCR (quantitative real-time PCR) assays using the adjacent normal tissue mRNA levels as an internal control. The most significantly altered genes in diabetic tumor samples were largely different from those in non-diabetic ones, implying that T2DM profoundly alters the expression of signaling genes and presumably the biological characteristics of CRC.

scholarly journals Altered Expression of Cadherin-8 and Cadherin-11 in Neural Circuit Development: Implications for Autism

2020 ◽  
Author(s):  
Jeannine A. Frei ◽  
Robert F. Niescier ◽  
Morgan S. Bridi ◽  
Madel Durens ◽  
Jonathan E. Nestor ◽  
...  
Keyword(s):  
Knockout Mice ◽  
Hippocampal Neurons ◽  
Neural Circuit ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Autism Spectrum ◽  
Synaptic Activity ◽  
Classical Type ◽  
Altered Expression ◽  
Expression Levels

AbstractAutism spectrum disorder (ASD) is a neurological condition characterized by difficulties in social interaction, communication, and behavior. The classical type II cadherins cadherin-8 (Cdh8, CDH8) and cadherin-11 (Cdh11, CDH11) have been implicated as autism risk gene candidates. To explore the role of cadherins in the etiology of autism, we investigated their expression patterns during mouse brain development and analyzed their functions using Cdh11 knockout mice. Expression of cadherin-8 and cadherin-11 was developmentally regulated and enriched in cortex, hippocampus, and thalamus/striatum during the peak of dendrite formation and synaptogenesis. Cadherin-8 preferentially localized to excitatory synapses where it interacted with neuroligin-1. Levels of cadherin-8, neuroligin-1, and PSD-95 were all significantly increased in Cdh11 knockout brains. Additionally, Cdh11-/- hippocampal neurons exhibited increased dendritic complexity along with altered neuronal and synaptic activity. Similar to the expression profiles in Cdh11 knockout mice, induced pluripotent stem cell (iPSC)-derived cortical neural precursor cells (NPCs) and cortical organoids generated from individuals with autism showed elevated CDH8 expression levels while CDH11 expression levels were decreased. Together, these results strongly suggest that cadherin-8 and cadherin-11 are involved in regulating the development of neuronal circuitry and that alterations in the expression levels of cadherin-8 and cadherin-11 may contribute to the etiology of autism.

scholarly journals Identifying Novel Glioma-Associated Noncoding RNAs by Their Expression Profiles

2017 ◽  
Vol 2017 ◽  
pp. 1-18 ◽  
Author(s):  
Alenka Matjašič ◽  
Mojca Tajnik ◽  
Emanuela Boštjančič ◽  
Mara Popović ◽  
Boštjan Matos ◽  
...  
Keyword(s):  
Expression Profiles ◽  
Expression Patterns ◽  
Correct Diagnosis ◽  
Noncoding Rnas ◽  
Protein Coding ◽  
Altered Expression ◽  
Expression Levels ◽  
Additional Information ◽  
Primary Brain Tumours ◽  
Mirnas Expression

Long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) play a significant role in cancer development as regulators of protein-coding genes. Their dysregulation was in some extent already associated with glioma, the most aggressive primary brain tumours in adults. The correct diagnosis and treatment selection due to high tumour heterogeneity might be difficult and inadequate, resulting in poor prognosis. Studies of expression patterns of noncoding RNAs (ncRNAs) could provide useful insight in glioma molecular development. We used the qPCR approach to screen and investigate the expression of lncRNAs that were previously deregulated in other cancer types. The study showed altered expression levels for numerous lncRNAs across histologically different glioma samples. Validation of few lncRNAs showed association of expression levels with histological subtype and/or malignancy grade. We also observed deregulated and subtype-distinctive expression for four lncRNA-associated miRNAs. Expression of few lncRNAs and miRNA was also associated with patients’ survival, showing potential prognostic value. Several ncRNAs, some already related to glioma and some, to the best of our knowledge, investigated for the first time, might be of greater importance in glioma molecular development and progression. Finding the subtype-specific lncRNA and/or miRNA expression patterns may contribute additional information for a more objective classification.

scholarly journals Characterization and Functional Divergence of a Novel DUF668 Gene Family in Rice Based on Comprehensive Expression Patterns

Genes ◽  
2019 ◽  
Vol 10 (12) ◽  
pp. 980
Author(s):  
Hua Zhong ◽  
Hongyu Zhang ◽  
Rong Guo ◽  
Qiang Wang ◽  
Xiaoping Huang ◽  
...  
Keyword(s):  
Gene Family ◽  
Expression Profiles ◽  
Functional Divergence ◽  
Expression Patterns ◽  
Gene Duplications ◽  
Altered Expression ◽  
Domain Of Unknown Function ◽  
Motif Composition ◽  
Conserved Gene

The domain of unknown function (DUF) superfamily encodes proteins of unknown functions in plants. Among them, DUF668 family members in plants possess a 29 amino-acid conserved domain, and this family has not been described previously. Here, we report this plant-specific novel DUF668 gene family containing 12 OsDUF668 genes in rice (Oryza sativa) and 91 DUF668s for the other seven plant species. In our study, DUF668 genes were present in both dicot and monocot plants, indicating that DUF668 is a conserved gene family that originated by predating the dicot–monocot divergence. Based on the gene structure and motif composition, the DUF668 family consists of two distinct clades, I and II in the phylogenetic tree. Remarkably, OsDUF668 genes clustered on the chromosomes merely show close phylogenetic relationships, suggesting that gene duplications or collinearity seldom happened. Cis-elements prediction display that over 80% of DUF668s contain phytohormone and light responsiveness factors. Further comprehensive experimental analyses of the OsDUF668 family are implemented in 22 different tissues, five hormone treatments, seven environmental factor stresses, and two pathogen-defense related stresses. The OsDUF668 genes express ubiquitously in analyzed rice tissues, and seven genes show tissue-specific high expression profiles. All OsDUF668s respond to drought, and some of Avr9/Cf-9 rapidly elicited genes resist to salt, wound, and rice blast with rapidly altered expression patterns. These findings imply that OsDUF668 is essential for drought-enduring and plant defense. Together, our results bring the important role of the DUF668 gene family in rice development and fitness to the fore.

Rituximab Plus Chlorambucil As Initial Treatment for Elderly Patients with Chronic Lymphocytic Leukemia (CLL): Effect of Pre-Treatment Biological Characteristics and Gene Expression Patterns on Response to Treatment

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 294-294 ◽  
Author(s):  
Robin Foa ◽  
Stefania Ciolli ◽  
Francesco Di Raimondo ◽  
Giovanni Del Poeta ◽  
Francesco Lauria ◽  
...  
Keyword(s):  
Gene Expression ◽  
Elderly Patients ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Gene Expression Signature ◽  
Standard Of Care ◽  
Response To Treatment ◽  
Induction Treatment ◽  
Induction Phase ◽  
Pre Treatment

Abstract Abstract 294 Rituximab plus fludarabine/cyclophosphamide (R-FC) is currently the standard of care for fit patients with untreated or relapsed CLL. However, patients with CLL are predominantly an elderly population and many of these patients may have comorbidities that make them less suitable to receive fludarabine-containing therapy. Chlorambucil-based treatments are frequently used for these patients despite the fact that clinical benefits are limited. There is a need for well-tolerated and more efficacious treatment regimens for these patients. The ML21445 study evaluated the combination of rituximab and chlorambucil (R-chlorambucil) as first-line treatment for patients with CLL considered ineligible for treatment with the current standard of care, R-FC. Patients aged >65 years (or 60–65 years and ineligible for fludarabine) were treated with eight 28-day cycles of chlorambucil (8 mg/m2/day Days 1–7) with rituximab administered on Day 1 of cycle 3 (375 mg/m2) and cycles 4–8 (500 mg/m2). Patients with a response at the end of induction were randomized to rituximab maintenance therapy (375 mg/m2 every 8 weeks for 2 years) or observation. The induction phase of the study is complete while the maintenance phase is still ongoing. The overall response rate (ORR) in 85 patients who received at least one dose of rituximab during induction was 81.2% (n = 69) with 16.5% (n = 14) achieving a complete response (CR) and 2.4% (n = 2) a CR with incomplete bone marrow recovery (CRi). ORR and CR rates were similar across the different Binet stages (ORR: Binet A 86.4%, Binet B 79.6%, Binet C 78.6%) and age categories (ORR: 60–64 years 84.6%, 65–69 years 85.2%, 70–74 years 75.0%, ≥75 years 81.0%). Two of four patients aged ≥80 years responded to induction treatment. Logistic regression analysis revealed no correlation between known biological prognostic factors – CD38, cytogenetics, IGHV mutational status, ZAP-70, thymidine kinase, soluble CD23, and beta-2 microglobulin – and response to treatment. To further investigate possible factors influencing response, pre-treatment patterns of gene expression were analyzed in different patient subgroups. Material was available for 62 patients, including 16 with CR/CRi, 41 partial responders and 5 non-responders. In an exploratory analysis, mRNA expression was examined using Affymetrix® Human Genome U133 microarrays. This revealed marked differences in pre-treatment gene expression profiles between response groups. Non-responders showed a homogeneous gene expression signature involving up-modulation of transcripts involved in anti-apoptotic and pro-proliferative pathways, including K-ras and N-ras. CR/CRi patients also showed a homogeneous pattern of gene expression that was clearly distinct from non-responding patients, while patients with a partial response showed a more heterogeneous pattern of gene expression before treatment. These initial findings reflect the heterogeneity of CLL and suggest that microarray analysis of gene expression may be useful in predicting response to R-chlorambucil in elderly patients with CLL. Disclosures: Foa: Roche: Consultancy, Speakers Bureau. Cuneo:Roche: Consultancy, Speakers Bureau. Montillo:Roche: Membership on an entity's Board of Directors or advisory committees. Alietti:Roche: Employment. Runggaldier:Roche: Employment. Gamba:Roche Italia: Employment.

scholarly journals Identification of microRNA expression patterns and definition of a microRNA/mRNA regulatory network in distinct molecular groups of multiple myeloma

Blood ◽  
2009 ◽  
Vol 114 (25) ◽  
pp. e20-e26 ◽  
Author(s):  
Marta Lionetti ◽  
Marta Biasiolo ◽  
Luca Agnelli ◽  
Katia Todoerti ◽  
Laura Mosca ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Mirna Expression ◽  
Plasma Cells ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Target Prediction ◽  
Primary Tumors ◽  
Altered Expression ◽  
Genome Wide ◽  
Definition Of

Abstract To date, little evidence of miRNA expression/deregulation in multiple myeloma has been reported. To characterize miRNA in the context of the major multiple myeloma molecular types, we generated miRNA expression profiles of highly purified malignant plasma cells from 40 primary tumors. Furthermore, transcriptional profiles, available for all patients, were used to investigate the occurrence of miRNA/predicted target mRNA pair anticorrelations, and the miRNA and genome-wide DNA data were integrated in a subset of patients to evaluate the influence of allelic imbalances on miRNA expression. Differential miRNA expression patterns were identified, which were mainly associated with the major IGH translocations; particularly, t(4;14) patients showed specific overexpression of let-7e, miR-125a-5p, and miR-99b belonging to a cluster at 19q13.33. The occurrence of other lesions (ie, 1q gain, 13q and 17p deletions, and hyperdiploidy) was slightly characterized by specific miRNA signatures. Furthermore, the occurrence of several allelic imbalances or loss of heterozygosity was found significantly associated with the altered expression of miRNAs located in the involved regions, such as let-7b at 22q13.31 or miR-140-3p at 16q22. Finally, the integrative analysis based on computational target prediction and miRNA/mRNA profiling defined a network of putative functional miRNA-target regulatory relations supported by expression data.

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