The Predominant microRNAs in β-cell Clusters for Insulin Regulation and Diabetic Control

2020 ◽  
Vol 21 (7) ◽  
pp. 722-734
Author(s):  
Adele Soltani ◽  
Arefeh Jafarian ◽  
Abdolamir Allameh
Keyword(s):  
Mirna Expression ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Diabetic Control ◽  
In Vitro Proliferation ◽  
Cell Functions ◽  
Mirna Expression Profiles ◽  
Multiple Processes ◽  
The Impact

micro (mi)-RNAs are vital regulators of multiple processes including insulin signaling pathways and glucose metabolism. Pancreatic β-cells function is dependent on some miRNAs and their target mRNA, which together form a complex regulative network. Several miRNAs are known to be directly involved in β-cells functions such as insulin expression and secretion. These small RNAs may also play significant roles in the fate of β-cells such as proliferation, differentiation, survival and apoptosis. Among the miRNAs, miR-7, miR-9, miR-375, miR-130 and miR-124 are of particular interest due to being highly expressed in these cells. Under diabetic conditions, although no specific miRNA profile has been noticed, the expression of some miRNAs and their target mRNAs are altered by posttranscriptional mechanisms, exerting diverse signs in the pathobiology of various diabetic complications. The aim of this review article is to discuss miRNAs involved in the process of stem cells differentiation into β-cells, resulting in enhanced β-cell functions with respect to diabetic disorders. This paper will also look into the impact of miRNA expression patterns on in vitro proliferation and differentiation of β-cells. The efficacy of the computational genomics and biochemical analysis to link the changes in miRNA expression profiles of stem cell-derived β-cells to therapeutically relevant outputs will be discussed as well.

scholarly journals MicroRNA Expression Profiles in Superficial Esophageal Squamous Cell Carcinoma before Endoscopic Submucosal Dissection: A Pilot Study

2021 ◽  
Vol 22 (9) ◽  
pp. 4789
Author(s):  
Shintaro Fujihara ◽  
Hideki Kobara ◽  
Noriko Nishiyama ◽  
Kayo Hirose ◽  
Hisakazu Iwama ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Endoscopic Submucosal Dissection ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Mirna Expression ◽  
Expression Profiles ◽  
Normal Tissues ◽  
Mirna Expression Profiles

Esophageal squamous cell carcinoma (ESCC) has a poor prognosis when diagnosed at an advanced stage, and early detection and treatment are essential to improve survival. However, intraobserver and interobserver variation make the diagnosis of superficial ESCC difficult, and suitable biomarkers are urgently needed. Here, we compared the microRNA (miRNA) expression profiles of superficial ESCC tissues and adjacent normal tissues obtained immediately before esophageal endoscopic submucosal dissection. We found that ESCC and normal tissues differed in their miRNA expression profiles. In particular, miR-21-5p and miR-146b-5p were significantly upregulated and miR-210-3p was significantly downregulated in tumor tissues compared with normal tissues. We also detected significant associations between miRNA expression and ESCC invasion depth and lymphovascular invasion. The same differential expression of miR-21-5p, miR-146b-5p, and miR-210-3p was detected in ESCC cell lines compared with normal esophageal epithelial cells in vitro. However, transfection of ESCC cells with miR-210-3p and miR-21-5p mimics or inhibitors had partial effects on cell proliferation and invasion in vitro. These results indicate that miRNA expression is significantly deregulated in superficial ESCC, and suggest that the potential contribution of differentially expressed miRNAs to the malignant phenotype should be further investigated.

scholarly journals MicroRNA expression patterns associated with hyperfunctioning and non-hyperfunctioning phenotypes in adrenocortical adenomas

2014 ◽  
Vol 170 (4) ◽  
pp. 583-591 ◽  
Author(s):  
David Velázquez-Fernández ◽  
Stefano Caramuta ◽  
Deniz M Özata ◽  
Ming Lu ◽  
Anders Höög ◽  
...  
Keyword(s):  
Mirna Expression ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Gene Mutations ◽  
Mirna Expression Profile ◽  
Differentially Expressed ◽  
Adrenocortical Adenoma ◽  
Tumor Subtypes ◽  
Mirna Expression Profiles ◽  
Differentially Expressed Mirnas

BackgroundThe adrenocortical adenoma (ACA) entity includes aldosterone-producing adenoma (APA), cortisol-producing adenoma (CPA), and non-hyperfunctioning adenoma (NHFA) phenotypes. While gene mutations and mRNA expression profiles have been partly characterized, less is known about the alterations involving microRNA (miRNA) expression.AimTo characterize miRNA expression profile in relation to the subtypes of ACAs.Subjects and methodsmiRNA expression profiles were determined in 26 ACAs (nine APAs, ten CPAs, and seven NHFAs) and four adrenal references using microarray-based screening. Significance analysis of microarrays (SAM) was carried out to identify differentially expressed miRNAs between ACA and adrenal cortices or between tumor subtypes. Selected differentially expressed miRNAs were validated in an extended series of 43 ACAs and ten adrenal references by quantitative RT-PCR.ResultsAn hierarchical clustering revealed separate clusters for APAs and CPAs, while the NHFAs were found spread out within the APA/CPA clusters. When NHFA was excluded, the clustering analysis showed a better separation between APA and CPA. SAM analysis identified 40 over-expressed and three under-expressed miRNAs in the adenomas as compared with adrenal references. Fourteen miRNAs were common among the three ACA subtypes. Furthermore, we found specific miRNAs associated with different tumor phenotypes.ConclusionThe results suggest that miRNA expression profiles can distinguish different subtypes of ACA, which may contribute to a deeper understanding of ACA development and potential therapeutics.

scholarly journals Effects of Short-time Exposure to Atrazine on miRNA Expression Profiles in the Gonad of Common Carp (Cyprinus carpio)

2018 ◽  
Author(s):  
Fang Wang ◽  
Qian-wen Yang ◽  
Wen-Jie Zhao ◽  
Qi-Yan Du ◽  
Zhong-Jie Chang
Keyword(s):  
Common Carp ◽  
Cyprinus Carpio ◽  
Mirna Expression ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Expression Profiles ◽  
Endocrine Disrupting Chemical ◽  
Endocrine Disrupting ◽  
Mirna Expression Profiles

ABSTRACTMicroRNAs (miRNAs) are endogenous small non-coding RNAs that negatively regulate gene expression by targeting specific mRNAs; they are involved in the modulation of important mRNA networks involved in toxicity. Atrazine is a known endocrine-disrupting chemical, whose molecular mechanisms are unknown. In this study, common carp (Cyprinus carpio) gonads at two key developmental stages were exposed to 0.428 ppb atrazine for 24 h in vitro. MiRNA expression profiles were analysed to identify miRNAs related to gonad development and to reveal the atrazine mechanisms interfering with gonad differentiation. Atrazine exposure caused significant alteration of multiple miRNAs. Compared with the juvenile ovary, more miRNAs were down-regulated in juvenile testis, some of these down-regulated miRNAs target the steroid hormone biosynthesis pathway related-genes. Predicted target genes of differently-expressed miRNAs after exposure to atrazine were involved in many reproductive biology signalling pathways. We suggest that these target genes may have important roles in atrazine-induced reproductive toxicity by altering miRNAs expression. Our results also indicate that atrazine can up-regulate aromatase expression through miRNAs, which supports the hypothesis that atrazine has endocrine-disrupting activity by altering the expression of genes of the Hypothalamus-Pituitary-Gonad axis through its corresponding miRNAs. This study tells us the following conclusions: 1. Atrazine exposure results in significant alterations of miRNAs whose predicted target genes are associated with reproductive processes. 2. In the primordial gonad, atrazine promoted the expression of early gonad-determining genes by decreasing specific miRNAs. 3. In the juvenile gonad, atrazine promoted the biosynthesis of steroid hormones.

scholarly journals Differential Leukocyte miRNA Responses Following Pan T Cell, Allorecognition and Allosecretome-Based Therapeutics Activation

2019 ◽  
Author(s):  
Xining Yang ◽  
Wendy M. Toyofuku ◽  
Mark D. Scott
Keyword(s):  
T Cell ◽  
Autoimmune Diseases ◽  
T Cell Activation ◽  
Mirna Expression ◽  
Cell Activation ◽  
Expression Profiles ◽  
Immunomodulatory Activity ◽  
Mirna Expression Profiles

Abstract Background: Effective immunomodulation of T cell responses is critical in treating both autoimmune diseases and cancer. Our previous studies have demonstrated that nanoscale bioengineering of cell surfaces with methoxypolyethylene glycol (mPEG) induces a potent tolerogenic immunomodulatory effect. Moreover, secretomes derived from mPEG- or control mixed lymphocyte alloactivation assays also exerted potent immunomodulatory activity that was mediated by microRNAs (miRNA). In this study, the immunomodulatory effects of Pan T cell activators (PHA and anti-CD3/CD28), alloactivation (MHC-disparate donors; ± mPEG grafting) and biomanufactured miRNA-based allo-secretome therapeutics (SYN, TA1, IA1 and IA2) were examined on T cell proliferation, subset differentiation and leukocyte miRNA expression profiles of resting human PBMC. Results: In contrast to Pan T cell activation, allorecognition and the pro-inflammatory IA1 secretome product induced increasingly controlled proliferation of resting PBMC. The differential effects of the activation strategies were also apparent in T cell differentiation and the Teff:Treg ratio and in the miRNA expression profiles noted in the treated PBMC. In contrast, the mPEG-PBMC and TA1 secretome products inhibited alloproliferation. Importantly, the activation strategies exerted significantly different miRNA expression in the treated leukocytes that was associated with differences in proliferation and cellular differentiation. Conclusions: Immunomodulatory secretome-derived, miRNA-enriched, therapeutics can be reproducibly biomanufactured that will induce the specific bioregulatory events necessary to induce the differentiation of naïve T cells to produce a tolerogeneic (TA1) or inflammatory (IA1) response both in vitro and in vivo. The successful development and biomanufacturing of immunomodulatory, miRNA-enriched, secretome biotherapeutics may provide potent tools for the systemic treatment of autoimmune diseases or enhancing the endogenous immune response to cancer while reducing the potential adverse risks of more non-specific immunomodulatory approaches.

Comparing mRNA and sncRNA profiles during the maternal-to-embryonic transition in bovine IVF and scNT embryos

2021 ◽  
Author(s):  
Jocelyn M Cuthbert ◽  
Stewart J Russell ◽  
Irina A Polejaeva ◽  
Qinggang Meng ◽  
Kenneth L White ◽  
...  
Keyword(s):  
Mirna Expression ◽  
Large Scale ◽  
Expression Profiles ◽  
Developmental Competence ◽  
Messenger Rnas ◽  
Aberrant Expression ◽  
Rna Transcripts ◽  
Mrna Targets ◽  
Mirna Expression Profiles

Abstract Production of embryos with high developmental competence by somatic cell nuclear transfer (scNT) is far less efficient than for in vitro fertilized (IVF) embryos, likely due to an accumulation of errors in genome reprogramming that results in aberrant expression of RNA transcripts, including messenger RNAs (mRNA) and, possibly, microRNAs (miRNA). Thus, our objectives were to use RNAseq to determine the dynamics of mRNA expression in early developing scNT and IVF embryos in the context of the maternal-to-embryonic transition (MET) and to correlate apparent transcriptional dysregulation in cloned embryos with miRNA expression profiles. Comparisons between scNT and IVF embryos indicated large scale transcriptome differences, which were most evident at the 8-cell and morula stages for genes associated with biological functions critical for the MET. For two miRNAs previously identified as differentially expressed in scNT morulae, miR-34a and miR-345, negative correlations with some predicted mRNA targets were apparent, though not widespread among the majority of predicted targets. Moreover, although large-scale aberrations in expression of mRNAs were evident during the MET in cattle scNT embryos, these changes were not consistently correlated with aberrations in miRNA expression at the same developmental stage, suggesting that other mechanisms controlling gene expression may be involved.

scholarly journals Comprehensive Analysis of microRNA Profiles in Organoids Derived from Human Colorectal Adenoma and Cancer

Digestion ◽  
2021 ◽  
pp. 1-10
Author(s):  
Hiroshi Nagai ◽  
Masatake Kuroha ◽  
Tomoyuki Handa ◽  
Hideaki Karasawa ◽  
Shinobu Ohnuma ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Mirna Expression ◽  
Expression Profiles ◽  
Cell Communication ◽  
Colorectal Adenomas ◽  
Mirna Expression Profiles ◽  
Exosomal Mirna ◽  
The Impact ◽  
First Time ◽  
Ht 29

Introduction: Exosomes are membrane-enclosed nanovesicles, which are increasingly being recognized as important cell communication components for their role in transmitting microRNAs (miRNAs). No previous study has addressed the exosomal miRNA profile in colorectal adenomas (CRAs) because the long-term culture of CRA is challenging. This study aimed to identify the miRNA signature in organoid exosomes derived from human CRA and colorectal cancer (CRC) samples. Methods: Organoid cultures were developed from resected colorectal tissues of patients with CRA or CRC undergoing surgery or endoscopic mucosal resection. Exosomes were prepared from the conditioned medium of the organoids. miRNAs were prepared from the exosomes and their source organoids. The miRNA expression profiles were compared using microarray analysis. The impact of alteration of miRNA expression on cell proliferation was examined using miRNA mimics or inhibitors in HT-29 human CRC cells. Results: We established 6 organoid lines from CRC and 8 organoid lines from CRA. Exosomal miRNA signatures were different between the organoids derived from CRA and CRC. Both exosomal and cellular miR-1246 expressions were upregulated in CRC-derived organoids compared to their expression in CRA-derived organoids. Alteration of miR-1246 expression by the miR-1246 mimic or inhibitor increased or decreased cell proliferation in HT-29 cells, respectively. Conclusions: We report for the first time the miRNA profiles of exosomes in CRA- and CRC-derived organoids. The upregulation of miR-1246 might play a role in increased cell proliferation in the process of CRA-carcinoma transition.

MicroRNA Expression Profiling Characterize Diffuse Large B-Cell Lymphomas and Follicular Lymphomas.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3186-3186
Author(s):  
Anja Roehle ◽  
Kai P. Hoefig ◽  
Dirk Repsilber ◽  
Christoph Thorns ◽  
Kai O. Wesche ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
B Cell ◽  
Mirna Expression ◽  
Germinal Center ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Mirna Expression Profiles ◽  
Proliferation And Differentiation ◽  
Follicular Lymphomas ◽  
Large B Cell

Abstract A new and powerful tool for classification and understanding the biology of human lymphomas is microRNA (miRNA) expression profiling. MiRNAs comprise a class of approximately 1000 RNA species, which are thought to directly regulate the expression of ∼30% of the transcripts of the human genome on a posttranscriptional level. An important regulatory role of miRNAs has been implicated in biological processes such as cell proliferation and differentiation, fat metabolism, insulin secretion and hematopoiesis. Recent studies indicate that miRNAs are mechanistically involved in the development of various human malignancies and therefore represent a promising new class of biomarkers. We evaluated the miRNA expression profiles of 58 Diffuse Large B-Cell Lymphomas (DLBCL), 46 Follicular Lymphomas (FL) and 7 lymph nodes with chronic lymphadenitis. A quantitative PCR-based method was used to determine the expression levels of 157 miRNA species. The analysis was performed exclusively on FFPE tissues, which are traditionally inapt to molecular analysis. It was possible to clearly distinguish malignant and non-malignant tissues by miRNA expression patterns. We found 34 differentially expressed miRNAs by comparing DLBCL and lymph nodes, 25 miRNAs by comparing FL and lymph nodes and 55 by comparing DLBCL and FL. It was noticeable that the miRNA expression profiles of FL and lymph nodes are more similar compared to miRNA expression profiles of DLBCL. We were also interested to find out whether it is possible to classify the DLBCL cases in germinal center-like DLBCL (GCB-DLBCL) and Non-germinal center-like DLBCL (Non-GCB-DLBCL) based on miRNA expression patterns. We used the immunohistochemical classification, published by Hans et al., to identify both subgroups (Hans CP, Weisenburger DD et al. Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. Blood. 2004; 103:275–282). Comparing miRNA expression profiles of GCB and Non-GCB cases of DLBCL, 8 miRNAs were found to be differentially expressed using the partial least squares discriminant analysis (PLS-DA). However, using a cross-validation approach it was not possible to predict the GCB status on the basis of miRNA expression patterns. Similar to Landgraf et al. we found a reduced miR-150 expression level in DLBCL in comparison to other closely related germinal center malignancies (Landgraf P, Ruscu M et al. A mammalian microRNA expression atlas based on small RNA library sequencing. Cell. 2007; 129:1401–1414). To determine the function of miR-150, Ramos cells were transfected with anti-miR-150 and an analysis of putative target proteins was carried out. It was possible to show a regulation of transcription factor v-myb/c-myc, which plays an important role in the control of proliferation and differentiation of hematopoietic progenitor cells, by miR-150. Moreover, miRNA profiles of DLBCL from a randomized trail will be compared to survival data in the future.

scholarly journals Mechanistic Basis of Arsenic Induced Carcinogenesis: Differential miRNA Expression

2022 ◽  
Author(s):  
Placheril J. John ◽  
Navneet Kumar
Keyword(s):  
Cancer Progression ◽  
Mirna Expression ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Inorganic Arsenic ◽  
Ros Generation ◽  
Mirna Expression Profiles ◽  
Mechanistic Basis

Abstract Arsenic, a toxic metalloid, provokes many detrimental consequences to human health. It is prevalent in earth's crust and poses a major threat to humans globally. Inorganic arsenic exposure occurs mainly via drinking water or food and is metabolized in mammals to form organic metabolites/ end products. Chronic exposure to arsenic causes lung, skin and urinary bladder cancers and increases the risks of liver, kidney and prostate cancers. Arsenic-induced ROS generation, disturbances in several signaling pathways, DNA repair inhibition, chromosomal aberrations, and epigenetic changes including alterations in DNA methylation, histone modifications and differential miRNA expression profiles are involved in cancer progression, and malignant transformation. However, details of arsenic-induced carcinogenesis and molecular mechanisms involved are still remaining obscure. MicroRNAs are post-transcriptional gene expression regulators and themselves may act as oncogenes and tumor suppressor genes. Differential miRNA expression is implicated in several human cancers. This review covers general mechanistic basis of arsenic-induced carcinogenesis, explores recent in-vitro, in-vivo and cohort studies on differential miRNA expression profiles and shares associated molecular mechanistic data on miRNA dysregulation and their functional consequences leading to arsenic induced tumorigenesis, metastasis and cancer, also discusses the future directions.

scholarly journals MicroRNA Involvement in Osteosarcoma

Sarcoma ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Eisuke Kobayashi ◽  
Francis J. Hornicek ◽  
Zhenfeng Duan
Keyword(s):  
Mirna Expression ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Therapeutic Targets ◽  
Research Field ◽  
Genome Wide ◽  
Mirna Expression Profiles ◽  
Novel Biomarkers

Osteosarcoma (OS) is the most common primary malignant bone tumor, usually arising in the long bones of adolescents and young adults. While our knowledge of the molecular pathogenesis of OS has increased in recent years, we are still far from a comprehensive understanding of the molecular mechanisms of the disease, such as its tumorigenesis, specific mediators of disease progression, occurrence of chemoresistance, and development of metastasis. After the recent discovery of microRNAs (miRNAs), their critical roles in molecular biological processes have been of great interest in the cancer research field, including research on sarcomas. MiRNAs are highly conserved noncoding RNAs which play important roles as oncogenic or suppressive genes to simultaneously regulate multiple targets. Recent genome-wide screening using miRNA expression profiles has identified specific miRNA expression patterns that are associated with the biological and clinical properties of cancers. Additionally, miRNAs and their target genes or proteins can be potential novel biomarkers or therapeutic targets for cancer. However, there are several challenges that must be addressed in order to translate miRNA-based therapeutics to the clinical setting. In this review, we summarize the current understanding of the roles that miRNAs play in OS, and highlight their potential as biomarkers or therapeutic targets.

scholarly journals Inflammation-Mediated Regulation of MicroRNA Expression in Transplanted Pancreatic Islets

2012 ◽  
Vol 2012 ◽  
pp. 1-15 ◽  
Author(s):  
Valia Bravo-Egana ◽  
Samuel Rosero ◽  
Dagmar Klein ◽  
Zhijie Jiang ◽  
Nancy Vargas ◽  
...  
Keyword(s):  
Mirna Expression ◽  
Expression Profiles ◽  
Mirna Gene ◽  
Therapeutic Interventions ◽  
Integrated Analysis ◽  
Gene Target ◽  
Endogenous Expression ◽  
The Impact

Nonspecific inflammation in the transplant microenvironment results inβ-cell dysfunction and death influencing negatively graft outcome. MicroRNA (miRNA) expression and gene target regulation in transplanted islets are not yet well characterized. We evaluated the impact of inflammation on miRNA expression in transplanted rat islets. Islets exposedin vitroto proinflammatory cytokines and explanted syngeneic islet grafts were evaluated by miRNA arrays. A subset of 26 islet miRNAs was affected by inflammation bothin vivoandin vitro. Induction of miRNAs was dependent on NF-κB, a pathway linked with cytokine-mediated islet cell death. RT-PCR confirmed expression of 8 miRNAs. The association between these miRNAs and mRNA target-predicting algorithms in genome-wide RNA studies ofβ-cell inflammation identified 238 potential miRNA gene targets. Several genes were ontologically associated with regulation of insulin signaling and secretion, diabetes, and islet physiology. One of the most activated miRNAs was miR-21. Overexpression of miR-21 in insulin-secreting MIN6 cells downregulated endogenous expression of the tumor suppressor Pdcd4 and of Pclo, a Ca2+sensor protein involved in insulin secretion. Bioinformatics identified both as potential targets. The integrated analysis of miRNA and mRNA expression profiles revealed potential targets that may identify molecular targets for therapeutic interventions.

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