scholarly journals Profiling 25 Bone Marrow microRNAs in Acute Leukemias and Secondary Nonleukemic Hematopoietic Conditions

Biomedicines ◽  
2020 ◽  
Vol 8 (12) ◽  
pp. 607
Author(s):  
Igor B. Kovynev ◽  
Sergei E. Titov ◽  
Pavel S. Ruzankin ◽  
Mechti M. Agakishiev ◽  
Yuliya A. Veryaskina ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mirna Expression ◽  
Expression Profiles ◽  
Lymphoblastic Leukemia ◽  
Molecular Genetic ◽  
Mirna Expression Profile ◽  
Classification Systems ◽  
Acute Leukemias ◽  
Mirna Expression Profiles ◽  
Genetic Features

Introduction: The standard treatment of acute leukemias (AL) is becoming more efficacious and more selective toward the mechanisms via which to suppress hematologic cancers. This tendency in hematology imposes additional requirements on the identification of molecular-genetic features of tumor clones. MicroRNA (miRNA, miR) expression levels correlate with cytogenetic and molecular subtypes of acute leukemias recognized by classification systems. The aim of this work is analyzing the miRNA expression profiles in acute myeloblastic leukemia (AML) and acute lymphoblastic leukemia (ALL) and hematopoietic conditions induced by non-tumor pathologies (NTP). Methods: A total of 114 cytological samples obtained by sternal puncture and aspiration biopsy of bone marrow (22 ALLs, 44 AMLs, and 48 NTPs) were analyzed by real-time PCR regarding preselected 25 miRNAs. For the classification of the samples, logistic regression was used with balancing of comparison group weights. Results: Our results indicated potential feasibility of (i) differentiating ALL+AML from a nontumor hematopoietic pathology with 93% sensitivity and 92% specificity using miR-150:miR-21, miR-20a:miR-221, and miR-24:nf3 (where nf3 is a normalization factor calculated from threshold cycle values of miR-103a, miR-191, and miR-378); (ii) diagnosing ALL with 81% sensitivity and 81% specificity using miR-181b:miR-100, miR-223:miR-124, and miR-24:nf3; and (iii) diagnosing AML with 81% sensitivity and 84% specificity using miR-150:miR-221, miR-100:miR-24, and miR-181a:miR-191. Conclusion: The results presented herein allow the miRNA expression profile to de used for differentiation between AL and NTP, no matter what AL subtype.

MicroRNA Expression Profiles in Chronic Myelomonocytic Leukemia

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2699-2699
Author(s):  
Mehdi Nassiri ◽  
Joseph Olczyk ◽  
Samantha Knapp ◽  
Gail Vance ◽  
Anupama Tewari ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mirna Expression ◽  
Expression Profiles ◽  
Chronic Myelomonocytic Leukemia ◽  
Differentially Expressed ◽  
Cytogenetic Abnormalities ◽  
Normal Bone ◽  
Normal Reference ◽  
Mirna Expression Profiles ◽  
Myelomonocytic Leukemia

Abstract Chronic myelomonocytic leukemia (CMML) is a hematopoietic malignancy with hybrid myeloproliferative and myelodysplastic features. The diagnostic criteria for CMML are evolving with the progress of our knowledge on various genetic lesions involved in the pathogenesis of myeloid neoplasms. This shift, including molecular genetic lesions in the diagnosis process, is highlighted in updated 2008 WHO classification system, which excludes myeloproliferative neoplasms with PDGFRB rearrangement, monocytosis and eosinophilia from CMML category. Despite these recent advancements, CMML remains a heterogeneous group of diseases with variable patient outcomes and no well-defined targeted therapy. To further investigate the biological diversity of this disorder, we studied microRNA (miRNA) expression profiles, their relation to the diagnostic and clinical parameters in CMML, and compared these profiles to global miRNA expression in normal reference bone marrow samples. MicroRNAs are a class of non-coding RNA molecules that alter gene expression by targeting and blocking mRNA. The role of miRNAs in carcinogenesis is related to their targeting of messenger RNAs encoding for oncogenes and tumor suppressor genes. Bone marrow samples from 22 patients with CMML were included in the study. Median age of the patients was 71 years with a range from 39 to 92 years. There were 15 males and 7 females. Seventeen patients presented with CMML-1 (blasts less than 5% in peripheral blood and less than 10% of bone marrow differential count). The remaining patients showed CMML-2. Nine patients had WBC below 13×109/L defining a myelodysplastic type of CMML. Cytogenetic results were available in 20 patients. Fourteen patients demonstrated a normal karyotype. Normal pooled bone marrow samples were used as a reference. The total RNA was isolated using RecoverAll RNA extraction kit. Micoroarray studies were performed using Agilent human miRNA microarrays (version 1.0) containing probes for 470 human and 64 human viral miRNAs cataloged in the Sanger database v9.1. The results were analyzed using BRB array tool and Genesis software. Unsupervised hierarchical clustering discovered two different groups of CMML samples with patterns of miRNA expression distinct from normal bone marrows (oneway ANOVA). Twenty seven miRNAs were differentially expressed in normal bone marrow reference samples vs. CMML-1 and -2. There was an overlap in miRNA profiles between groups of CMML based on blast percentage (CMML-1 vs. CMML-2), WBC count (<13×109/L vs. ≥13×109/L) and presence or absence of cytogenetic abnormalities. However, using PAM algorithm the following miRNAs showed predictive power: hsa-miR-519b (in CMML-1 vs. 2); hsa-miR-15b and hsa-miR-432* (in groups of samples separated by a cut-off WBC of 13×109/L) and hsa-miR-223 (comparing CMML with and without cytogenetic abnormalities). In summary, significantly different miRNA profiles were seen in CMML as compared to normal reference bone marrow. Two distinct subgroups of CMML were defined by the miRNA expression profiles. Select miRNAs were differentially expressed in known biological and clinical subgroups of CMML. Further correlation of clinical and outcome data with subgroups of CMML defined by miRNA expression profiles will be presented.

Molecular Genetic Characterization of 3'-Deletion of MLL Gene in Infant Acute Leukemia.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2498-2498
Author(s):  
Grigory Tsaur ◽  
Olga Plekhanova ◽  
Alexander Popov ◽  
Tatyana Gindina ◽  
Yulia Olshanskaya ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Leukemia ◽  
Lymphoblastic Leukemia ◽  
Molecular Genetic ◽  
Fish Analysis ◽  
Long Distance ◽  
Mll Gene ◽  
Partner Gene ◽  
Genetic Features ◽  
Blast Cells

Abstract Abstract 2498 Background. MLL gene rearrangements are associated with unfavorable outcome in infant acute lymphoblastic leukemia (ALL) and have intermediate prognosis in infant acute myeloid leukemia (AML). Application of fluorescence in-situ hybridization (FISH) allows detecting not only conventional MLL rearrangements, but also concurrent 3'-deletion of MLL gene. However, detailed characteristics of infant leukemia carrying 3' MLL deletion remain unclear. Aim. To investigate molecular genetic features of MLL-rearranged infant acute leukemia with concurrent 3' MLL deletion. Methods. 64 patients (27 boys and 37 girls) aged from 1 day to 11 months (median 6.6 months) including 44 ALL patients, 18 AML patients, 1 patient with acute bilineage leukemia and 1 patient with acute undifferentiated leukemia were enrolled in the current study. Chromosome banding analysis was done according to standard procedure. FISH analysis using LSI MLL Dual Color, Break Apart Rearrangement Probe (Abbott Molecular, USA) was performed on at least 200 interphase nuclei and on all available metaphases. Presence of MLL rearrangements was detected by FISH, reverse-transcriptase PCR. In 29 cases long-distance inverse PCR was additionally performed. In case of MLL rearrangement presence standard FISH pattern was defined as simultaneous detection of 3 different fluorescent signals: 1 fused (orange) signal, 1 green signal derived from 3' part of MLL gene, 1 red signal from 5' end of MLL (1F1G1R). MLL rearrangements with concurrent 3' MLL deletion led to 1F1R FISH pattern formation due to lack of green signal. Results. FISH revealed MLL rearrangements in 73% of ALL cases that was higher than frequency of 11q23 translocations detected by conventional cytogenetics — 55%. In MLL-positive cases we found 38 patients (81%) with standard FISH pattern, 7 ones (15%) with concurrent 3'-deletion of MLL gene and 2 (4%) with complex MLL rearrangements. Among patients with 3' MLL deletions there were 1 case with 5' MLL duplication (1F2R) and 1 case with 5' MLL triplication (1F3R). Frequency of 3'-deletions were similar in ALL and AML patients (13% and 15%, respectively). We did not find more than one FISH pattern in bone marrow blast cells of each patient with 3' MLL deletion. In this cohort of patients all blast cells carried concurrent 3'-deletion of MLL gene. Moreover, percentage of blast cells carrying MLL rearrangements did not differ significantly between patients with standard FISH pattern (median 97%, range 22–100%) and 3'-deletion (median 83%, range 13–99%) (p=0.206). 3'-deletion of MLL was not associated with breakpoint position in MLL gene and type of translocation partner gene. MLL translocation partner genes detected in patients with 3' deletions were as follows AF4(n=2), MLLT3(n= 3), MLLT10(n=2). None of the patients with 3'-deletions had reciprocal fusion gene. Initial patients' characteristics (age, sex, WBC count, immunophenotype, CNS-status, type of MLL partner gene) and treatment response parameters (day 8 peripheral blood blast cell count, day 15 bone marrow status, day 36 remission achievement, minimal residual disease status at time point 4) did not differ significantly between 2 groups. Although cumulative incidence of relapse was lower in patients with 3'-deletion as compared to patients with standard FISH pattern (0.31±0.04 and 0.55±0.01, respectively), difference between these two groups was not statistically significant (p=0.359). Conclusion. In our work we characterized rare subgroup of infant MLL-rearranged acute leukemia carrying concurrent 3' MLL deletion. Our data provide additional information of molecular genetic features of acute leukemia in children younger than one year. Disclosures: No relevant conflicts of interest to declare.

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 MicroRNA expression profiling of carcinoma in situ cells of the testis

2012 ◽  
Vol 19 (3) ◽  
pp. 365-379 ◽  
Author(s):  
Guy Wayne Novotny ◽  
Kirstine C Belling ◽  
Jesper Bertram Bramsen ◽  
John E Nielsen ◽  
Jette Bork-Jensen ◽  
...  
Keyword(s):  
Germ Cell ◽  
Mirna Expression ◽  
Expression Profiles ◽  
Mirna Expression Profile ◽  
Human Testis ◽  
Germ Cell Tumours ◽  
Testicular Germ Cell ◽  
Adult Testis ◽  
Mirna Expression Profiles

Testicular germ cell tumours, seminoma (SE) and non-seminoma (NS), of young adult men develop from a precursor cell, carcinomain situ(CIS), which resembles foetal gonocytes and retains embryonic pluripotency. We used microarrays to analyse microRNA (miRNA) expression in 12 human testis samples with CIS cells and compared it with miRNA expression profiles of normal adult testis, testis with Sertoli-cell-only that lacks germ cells, testis tumours (SE and embryonal carcinoma (EC), an undifferentiated component of NS) and foetal male and female gonads. Principal components analysis revealed distinct miRNA expression profiles characteristic for each of the different tissue types. We identified several miRNAs that were unique to testis with CIS cells, foetal gonads and testis tumours. These included miRNAs from the hsa-miR-371–373 and -302–367 clusters that have previously been reported in germ cell tumours and three miRNAs (hsa-miR-96, -141 and -200c) that were also expressed in human epididymis. We found several miRNAs that were upregulated in testis tumours: hsa-miR-9, -105 and -182–183–96 clusters were highly expressed in SE, while the hsa-miR-515–526 cluster was high in EC. We conclude that the miRNA expression profile changes during testis development and that the miRNA profile of adult testis with CIS cells shares characteristic similarities with the expression in foetal gonocytes.

miRNA Profiling in Human Granulopoiesis and in Activated Neutrophils From Skin Window.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2136-2136
Author(s):  
Maria Torp Larsen ◽  
Christoffer Hother ◽  
Mattias Hager ◽  
Corinna Cavan Pedersen ◽  
Lars Jacobsen ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Bone Marrow ◽  
Inflammatory Response ◽  
Mirna Expression ◽  
Peripheral Blood ◽  
Expression Profiles ◽  
Cycle Arrest ◽  
Mirna Expression Profiles ◽  
Differentially Expressed Mirnas ◽  
Activated Neutrophils

Abstract Abstract 2136 Formation of polymorphonuclear neutrophils (PMN) is a tightly regulated process where the myeloid progenitor cells, myeloblasts (MBs), divide and mature in the bone marrow, along a well defined path. The cells pass through six well defined stages in differentiation ending up with the release of mature PMNs to peripheral blood (granulopoiesis). Expression of essential transcription factors such as RUNX1, C/EBP-a, and C/EBP-e during granulopoiesis has been shown to have great importance for correct neutrophil development. microRNAs (miRNAs) could be important players in the fine-tuning of transcription factor expression due to their ability to regulate protein synthesis. The function of neutrophils is to detect and destroy invading microorganisms. This involves activation of the PMNs in the blood stream causing a release of secretory vesicles and up-regulation of extracellular adhesion molecules followed by migration in the tissue towards the focus of inflammation. Expression of miRNAs might also be regulated during activation and diapedesis of the neutrophils in order to adapt the neutrophil to its new environment and function. A regulatory role for miRNAs has been demonstrated for several biological processes, such as proliferation, differentiation, inflammation and cancer, and dysregulation of miRNA expression has been shown to contribute to disease development. The purpose of this study was to determine the miRNA expression profiles during normal human granulopoiesis starting with the first identifiable granulocytic precursor cell (MB) and ending with activated neutrophils that have migrated into the tissue using an Affymetrix 2,0 miRNA microarray platform. We isolated four populations of cells: Myeloblasts (MB) and promyelocytes (PM), myelocytes (MC) and metamyelocytes (MM), and band cells (BC) and segmented cells (SC) from the bone marrow and PMNs from peripheral blood from three different donors. We found 135 differentially expressed miRNAs in granulopoiesis, which could be divided into six clusters according to their expression pattern. 87% of the 135 miRNAs were differentially regulated between the MB/PM (dividing cells) and the MC/MM stages (cessation of cell proliferation and initiation of terminal differentiation) and could imply a need for miRNA-mediated regulation of the many proteins involved in regulating this process. Interestingly, we also found two distinct clusters of miRNAs that were either up- or down-regulated only in the MC/MM population, indicating the importance of a specific temporary regulation of some proteins during neutrophil development. To determine miRNA expression profiles in activated granulocytes, we examined PMNs and activated neutrophils from skin window (i.e. PMNs migrated to a site of inflammation). We found seven differentially expressed miRNAs, - all of them up regulated in the activated neutrophils. Using microRNA target-prediction software, we found that miRNAs 155, 146a and 130a, all of which are strongly up-regulated in the MB/PM stage, have several targets in the IL1-receptor signalling cascade, indicating the importance of miRNA of dampening an innate immune response in immature neutrophil precursors. miR-146a, 155 and 130a also have predicted targets in either the TGF-βI or the TGF-βII receptor which inhibits proliferation when binding to TGF-β. This finding supports the proliferating profile for the MB/PM cells, and the shift towards cell cycle arrest when the cells differentiate to the next stage, where expression of these three miRNAs is low. miRNA-34c-3p is highly expressed only in the MC/MM stage and has verified targets in many different mRNAs involved in the regulation of cell cycle arrest. All the miRNAs that were up-regulated in the activated neutrophils have several predicted targets in the IL1R pathway, and some of them (miR-212, −132 and −297) have previously been shown to be important in regulating the inflammatory response. The study indicates that several different miRNAs have important roles in the regulation of normal granulopoiesis, and that miRNAs also might be part of a possible negative feed back loop in the inflammatory response in activated neutrophils. Grant acknowledgments: The Danish Cancer Society, Lundbeck foundation, Danish Medical Research Council, Brøchner Mortensen foundation Disclosures: No relevant conflicts of interest to declare.

Application of micro-RNA (miRNA) expression profiles for prognostication in low-risk endometrial carcinoma (LEC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5032-5032
Author(s):  
Johanne Ingrid Weberpals ◽  
Jaime Snowdon ◽  
Olga Bougie ◽  
Xiao Zhang ◽  
Victor Tron ◽  
...  
Keyword(s):  
Decision Tree ◽  
Mirna Expression ◽  
Expression Profiles ◽  
Mirna Expression Profile ◽  
Micro Rna ◽  
Primary Surgery ◽  
Formalin Fixed Paraffin ◽  
Mirna Expression Profiles ◽  
Formalin Fixed Paraffin Embedded ◽  
Stage 1

5032 Background: Reliably predicting which LEC patients are most likely to recur is a challenge for the clinician with implications on adjuvant therapy. MiRNAs have been exploited for diagnosis and prognostication in a number of malignancies. We hypothesize that miRNA expression profiles differ in tumors from patients with recurrence compared to those without recurrence. Methods: The inclusion criteria for this study are informed consent, stage 1 disease, grade 1 or 2 tumors and endometrioid histology. RNA was extracted from formalin-fixed paraffin-embedded tissues and miRNA profiling was done using Agilent Human miRNA. Differentially expressed miRNAs were identified using GeneSpring GX software and the two groups were compared using the student t-test. Results: The expression levels of 866 miRNAs were determined from LEC patients with recurrence (n=15) and without recurrence (n=16). The mean follow-up interval was 61.5 months. The average age of cancer diagnosis for patients with and without recurrence was 60.2 (range 42-75) and 59.7 (range 44-86), respectively (p=0.91). Three of 15 patients with recurrence and 6 of 16 patients without recurrence received adjuvant brachytherapy following their primary surgery (p=0.43). 17 miRNAs were identified which can distinguish between the tumors with recurrence and those without recurrence (p<0.05). MiR-146a, miR-18a, miR-222, and miR-30a showed the highest fold change difference (>5 fold) in the tumors with recurrence compared to that did not recur. A decision tree prediction model for recurrent LEC was developed where a miRNA cutoff was used as a branch in the decision tree. This model identified those patients who were most likely to recur based on the expression of 4 dysregulated miRNAs (miR-222, miR-361-3p, miR-181c and miR-125b). Conclusions: These preliminary results show the miRNA expression profile differs among LEC and can be used to distinguish an aggressive sub-group. Should future validation studies confirm this result, this information would be valuable in the design of a biomarker study to help decide which patients would benefit most from extended adjuvant treatment.

Machine learning-based multiple cancer detections with circulating miRNA profiles in the blood.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3037-3037
Author(s):  
Juntaro Matsuzaki ◽  
Yusuke Yamamoto ◽  
Ouyang Yi ◽  
Sandeep Ayyar ◽  
Ryo Miyajima ◽  
...  
Keyword(s):  
Machine Learning ◽  
Early Detection ◽  
Mirna Expression ◽  
Expression Profiles ◽  
Mirna Expression Profile ◽  
Diagnostic Methods ◽  
Serum Samples ◽  
Multiple Cancer ◽  
Mirna Expression Profiles ◽  
Cancer Types

3037 Background: Early detection of cancer is one of the most important unmet clinical demands. A wide variety of circulating microRNAs (miRNAs) that specifically indicate many types of cancer have been identified, and their miRNA expression profiles are considered as potential biomarkers. Therefore, circulating miRNAs may serve as a non-invasive liquid biopsy diagnostic tool for early detection of many types of cancer. Here, a novel blood-based diagnostic method combined with machine learning techniques is developed using the entire circulating miRNA expression repertoire in serum without prior selection of miRNA marker sets. Methods: To validate this diagnostic method, clinical serum samples from cancer patients with five types of cancer (breast cancer(272), colorectal cancer(239), lung cancer(223), stomach cancer(221) and pancreatic cancer(100)) and 289 non-cancer volunteers were collected. Serum samples were immediately processed and their small RNAs were extracted. The entire miRNA expression profile is analyzed via next generation sequencers. The resulting total miRNA expression profile was used to train machine learning models, including deep learning techniques, without prior selection of miRNAs by human intervention. The machine learning model was trained with a training set to test set ratio of 4:1 and was carefully monitored by 5-fold cross-validation to avoid overfitting. Results: The diagnostic model provided 88% accuracy for all five cancer types (mean). The overall average AUROC was 0.954. Especially for breast cancer, the machine learning model provided 90% accuracy and 91 % sensitivity at 90% specificity. The overall AUROC was 0.966. High sensitivity was obtained regardless of the stage of the cancers, indicating that the possibility of early detection of cancer is kept high. Conclusions: Circulating miRNAs can be informative biomarkers for the earliest cancer detection in combination with machine learning. Unlike other cancer diagnostic methods where only a handful number of biomarkers are considered, this novel miRNA diagnostic platform method that uses machine learning reads a large set of miRNA expression profiles and automatically extracts the specific patterns of miRNA expression for early detection of multiple cancer types. In addition, the main advantage of miRNA-based cancer diagnosis is that they are more sensitive even in the early stages of cancer, compared to other diagnostic methods, such as cell-free DNA diagnostics, where the sensitivity of many types of cancer in the early stages still remains low. This approach could be easily expanded to other cancer types. Given the potential value of early detection in fatal malignancies, further validation studies are justified in future population-based studies. Many cancer research institutes are currently conducting further clinical trials to validate this early cancer diagnosis based on miRNA expression profiles.

scholarly journals Effects of Herb-Partitioned Moxibustion on the miRNA Expression Profiles in Colon from Rats with DSS-Induced Ulcerative Colitis

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Yan Huang ◽  
Zhe Ma ◽  
Yun-hua Cui ◽  
Hong-sheng Dong ◽  
Ji-meng Zhao ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Mirna Expression ◽  
Target Genes ◽  
Tissue Injury ◽  
Expression Profiles ◽  
Mirna Expression Profile ◽  
The Body ◽  
Mirna Expression Profiles ◽  
Body Weights ◽  
Mirnas Expression

Objective.This study explored the mechanism of herb-partitioned moxibustion (HM) on dextran sulfate sodium- (DSS-) induced ulcerative colitis (UC) from the miRNA perspective.Methods.Rats were randomly divided into 3 groups [normal control (NC) group, UC model (UC) group, and herb-partitioned moxibustion (UCHM) group]. The UC and UCHM groups were administered 4% DSS for 7 days. The UCHM group received HM at the Tianshu (bilateral, ST25). The effect of HM on UC was observed and the miRNA expression profile in the colon tissues was analyzed.Results.Compared with the UC group, the body weights were significantly higher in the UCHM group on day 14 (P<0.001); the macroscopic colon injury scores and microscopic histopathology scores in the UCHM group decreased (P<0.05); and there were 15 differentially expressed miRNAs in the UCHM group. The changes in miR-184 and miR-490-5p expression levels on the UC were reversed by HM intervention. Validation using qRT-PCR showed that two miRNAs expression trend was consistent with the sequencing results.Conclusion.HM at ST25 might regulate miR-184 and miR-490-5p expression, act on the transcription of their target genes to regulate inflammatory signaling pathways, and attenuate inflammation and tissue injury in the colons of rats with DSS-induced UC.

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 &#946;-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 &#946;-cells functions such as insulin expression and secretion. These small RNAs may also play significant roles in the fate of &#946;-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 &#946;-cells, resulting in enhanced &#946;-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 &#946;-cells. The efficacy of the computational genomics and biochemical analysis to link the changes in miRNA expression profiles of stem cell-derived &#946;-cells to therapeutically relevant outputs will be discussed as well.

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