scholarly journals Marked TGF-β-regulated miRNA expression changes in both COPD and control lung fibroblasts

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
J. Ong ◽  
A. Faiz ◽  
W. Timens ◽  
M. van den Berge ◽  
M. M. Terpstra ◽  
...  
Keyword(s):  
Tissue Repair ◽  
Target Genes ◽  
Interaction Analysis ◽  
Differential Regulation ◽  
Lung Fibroblasts ◽  
Small Rna Sequencing ◽  
Mirna Regulation ◽  
Copd Patients ◽  
And Function ◽  
And Control

AbstractCOPD is associated with disturbed tissue repair, possibly due to TGF-β-regulated miRNA changes in fibroblasts. Our aim was to identify TGF-β-regulated miRNAs and their differential regulation and expression in COPD compared to control fibroblasts. Small RNA sequencing was performed on TGF-β-stimulated and unstimulated lung fibroblasts from 15 COPD patients and 15 controls. Linear regression was used to identify TGF-β-regulated and COPD-associated miRNAs. Interaction analysis was performed to compare miRNAs that responded differently to TGF-β in COPD and control. Re-analysis of previously generated Ago2-IP data and Enrichr were used to identify presence and function of potential target genes in the miRNA-targetome of lung fibroblasts. In total, 46 TGF-β-regulated miRNAs were identified in COPD and 86 in control fibroblasts (FDR < 0.05). MiR-27a-5p was the most significantly upregulated miRNA. MiR-148b-3p, miR-589-5p and miR-376b-3p responded differently to TGF-β in COPD compared to control (FDR < 0.25). MiR-660-5p was significantly upregulated in COPD compared to control (FDR < 0.05). Several predicted targets of miR-27a-5p, miR-148b-3p and miR-660-5p were present in the miRNA-targetome, and were mainly involved in the regulation of gene transcription. In conclusion, altered TGF-β-induced miRNA regulation and differential expression of miR-660-5p in COPD fibroblasts, may represent one of the mechanisms underlying aberrant tissue repair and remodelling in COPD.

VEGF synthesis is induced by prostacyclin and TGF-β in distal lung fibroblasts from COPD patients and control subjects: Implications for pulmonary vascular remodelling

Respirology ◽  
2017 ◽  
Vol 23 (1) ◽  
pp. 68-75 ◽  
Author(s):  
Gunilla Westergren-Thorsson ◽  
Mariam Bagher ◽  
Annika Andersson-Sjöland ◽  
Lena Thiman ◽  
Claes-Göran Löfdahl ◽  
...  
Keyword(s):  
Lung Fibroblasts ◽  
Vascular Remodelling ◽  
Control Subjects ◽  
Copd Patients ◽  
Distal Lung ◽  
And Control ◽  
Pulmonary Vascular Remodelling

scholarly journals Genome-Wide Expression Difference of MicroRNAs in Basal Cell Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Hai-Peng Wei ◽  
Song Zhan ◽  
Qing-An Zhu ◽  
Zhen-Juan Chen ◽  
Xian Feng ◽  
...  
Keyword(s):  
Basal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Basal Cell ◽  
Target Genes ◽  
Expression Profiles ◽  
Taqman Probe ◽  
Control Group ◽  
Small Rna Sequencing ◽  
Mirna Regulation ◽  
Genome Wide

Distinct expression of the miRNAs has rarely been explored in basal cell carcinoma (BCC) of skin, and the regulatory role of miRNAs in BCC development remains quite opaque. Here, we collected control tissues from adjacent noncancerous skin ( n = 15 ; control group) and tissues at tumor centers from patients with cheek BCC ( n = 15 ; BCC group) using punch biopsies. After six small RNA sequencing- (sRNA-seq-) based miRNA expression profiles were generated for both BCC and controls, including three biological replicates, we conducted comparative analysis on the sRNA-seq dataset, discovering 181 differentially expressed miRNAs (DEMs) out of the 1,873 miRNAs in BCCs. In order to validate the sRNA-seq data, expression of 15 randomly selected DEMs was measured using the TaqMan probe-based quantitative real-time PCR. Functional analysis of predicted target genes of DEMs in BCCs shows that these miRNAs are primarily involved in various types of cancers, immune response, epithelial growth, and morphogenesis, as well as energy production and metabolism, indicating that BCC development is caused, at least in part, by changes in miRNA regulation for biological and disease processes. In particular, the “basal cell carcinoma pathways” were found to be enriched by predicted DEM targets, and regulatory relationships between DEMs and their targeted genes in this pathway were further uncovered. These results revealed the association between BCCs and abundant miRNA molecules that regulate target genes, functional modules, and signaling pathways in carcinogenesis.

scholarly journals The Role and Function of microRNA in the Pathogenesis of Multiple Myeloma

Cancers ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1738 ◽  
Author(s):  
Hiroshi Handa ◽  
Yuki Murakami ◽  
Rei Ishihara ◽  
Kei Kimura-Masuda ◽  
Yuta Masuda
Keyword(s):  
Multiple Myeloma ◽  
Messenger Rna ◽  
Target Genes ◽  
Expression Patterns ◽  
Mirna Regulation ◽  
Coding Regions ◽  
Cancer Pathogenesis ◽  
Regulation Mechanisms ◽  
And Function ◽  
Role And Function

Recently, attention has been drawn to the role of non-coding regions of the genome in cancer pathogenesis. MicroRNAs (miRNAs) are small non-coding RNAs with 19–25 bases of length that control gene expression by destroying messenger RNA or inhibiting its translation. In multiple myeloma (MM), the expression of several miRNAs, such as miR-15a and miR-16, is markedly decreased and their target genes upregulated, suggesting their role as tumor-suppressing miRNAs. In contrast, miRNAs such as miR-21 and miR-221 are highly expressed and function as oncogenes (oncomiRs). In addition, several miRNAs, such as those belonging to the miR-34 family, are transcriptional targets of p53 and mediate its tumor-suppressive functions. Many miRNAs are associated with drug resistance, and the modulation of their expression or activity might be explored to reverse it. Moreover, miRNA expression patterns in either MM cells or serum exosomes have been shown to be good prognostic markers. miRNA regulation mechanisms have not been fully elucidated. Many miRNAs are epigenetically controlled by DNA methylation and histone modification, and others regulate the expression of epigenetic modifiers, indicating that miRNA and other epigenetic effectors are part of a network. In this review, we outlined the roles of miRNAs in MM and their potential to predict MM prognosis and develop novel therapies.

scholarly journals Distinct miRNA Signatures and Networks Discern Fetal from Adult Erythroid Differentiation and Primary from Immortalized Erythroid Cells

2021 ◽  
Vol 22 (7) ◽  
pp. 3626
Author(s):  
Panayiota L. Papasavva ◽  
Nikoletta Y. Papaioannou ◽  
Petros Patsali ◽  
Ryo Kurita ◽  
Yukio Nakamura ◽  
...  
Keyword(s):  
Mirna Expression ◽  
Regulatory Networks ◽  
Target Genes ◽  
Human Peripheral Blood ◽  
Expression Patterns ◽  
Erythroid Differentiation ◽  
Erythroid Cell ◽  
Small Rna Sequencing ◽  
Erythroid Cells ◽  
Mirna Regulation

MicroRNAs (miRNAs) are small non-coding RNAs crucial for post-transcriptional and translational regulation of cellular and developmental pathways. The study of miRNAs in erythropoiesis elucidates underlying regulatory mechanisms and facilitates related diagnostic and therapy development. Here, we used DNA Nanoball (DNB) small RNA sequencing to comprehensively characterize miRNAs in human erythroid cell cultures. Based on primary human peripheral-blood-derived CD34+ (hCD34+) cells and two influential erythroid cell lines with adult and fetal hemoglobin expression patterns, HUDEP-2 and HUDEP-1, respectively, our study links differential miRNA expression to erythroid differentiation, cell type, and hemoglobin expression profile. Sequencing results validated by reverse-transcription quantitative PCR (RT-qPCR) of selected miRNAs indicate shared differentiation signatures in primary and immortalized cells, characterized by reduced overall miRNA expression and reciprocal expression increases for individual lineage-specific miRNAs in late-stage erythropoiesis. Despite the high similarity of same-stage hCD34+ and HUDEP-2 cells, differential expression of several miRNAs highlighted informative discrepancies between both cell types. Moreover, a comparison between HUDEP-2 and HUDEP-1 cells displayed changes in miRNAs, transcription factors (TFs), target genes, and pathways associated with globin switching. In resulting TF-miRNA co-regulatory networks, major therapeutically relevant regulators of globin expression were targeted by many co-expressed miRNAs, outlining intricate combinatorial miRNA regulation of globin expression in erythroid cells.

scholarly journals MicroRNAs in the Neural Retina

2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
Kalina Andreeva ◽  
Nigel G. F. Cooper
Keyword(s):  
Transcription Factors ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Neural Retina ◽  
Posttranscriptional Gene Regulation ◽  
Long Time ◽  
Gene Transcripts ◽  
The Central Nervous System ◽  
And Function ◽  
And Control

The health and function of the visual system rely on a collaborative interaction between diverse classes of molecular regulators. One of these classes consists of transcription factors, which are known to bind to DNA and control the transcription activities of their target genes. For a long time, it was thought that the transcription factors were the only regulators of gene expression. More recently, however, a novel class of regulators emerged. This class consists of a large number of small noncoding endogenous RNAs, namely, miRNAs. The miRNAs compose an essential component of posttranscriptional gene regulation, since they ultimately control the fate of gene transcripts. The retina, as a part of the central nervous system, is a well-established model for unraveling the molecular mechanisms underlying neuronal and glial functions. Numerous recent efforts have been made towards identification of miRNAs and their inferred roles in the visual pathway. In this review, we summarize the current state of our knowledge regarding the expression and function of miRNA in the neural retina and we discuss their potential uses as biomarkers for some retinal disorders.

scholarly journals 27-Hydroxycholesterol accelerates cellular senescence in human lung resident cells

2016 ◽  
Vol 310 (11) ◽  
pp. L1028-L1041 ◽  
Author(s):  
Yuichiro Hashimoto ◽  
Hisatoshi Sugiura ◽  
Shinsaku Togo ◽  
Akira Koarai ◽  
Kyoko Abe ◽  
...  
Keyword(s):  
Cellular Senescence ◽  
Healthy Subjects ◽  
Tissue Repair ◽  
Airway Epithelial Cells ◽  
Lung Fibroblasts ◽  
Chronic Obstructive ◽  
Prostaglandin E ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients ◽  
Associated Proteins

Cellular senescence is reportedly involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). We previously showed that 27-hydroxycholesterol (27-OHC) is elevated in the airways of COPD patients compared with those in healthy subjects. The aim of this study was to investigate whether lung fibroblasts of COPD patients are senescent and to determine the effects of 27-OHC on senescence of lung resident cells, including fibroblasts and airway epithelial cells. Localization of senescence-associated proteins and sterol 27-hydroxylase was investigated in the lungs of COPD patients by immunohistochemical staining. To evaluate whether 27-OHC accelerates cellular senescence, lung resident cells were exposed to 27-OHC. Senescence markers and fibroblast-mediated tissue repair were investigated in the 27-OHC-treated cells. Expression of senescence-associated proteins was significantly enhanced in lung fibroblasts of COPD patients. Similarly, expression of sterol 27-hydroxylase was significantly upregulated in lung fibroblasts and alveolar macrophages in these patients. Treatment with the concentration of 27-OHC detected in COPD airways significantly augmented expression of senescence-associated proteins and senescence-associated β-galactosidase activity, and delayed cell growth through the prostaglandin E2-reactive nitrogen species pathway. The 27-OHC-treated fibroblasts impaired tissue repair function. Fibroblasts from lungs of COPD patients showed accelerated senescence and were more susceptible to 27-OHC-induced cellular senescence compared with those of healthy subjects. In conclusion, 27-OHC accelerates cellular senescence in lung resident cells and may play a pivotal role in cellular senescence in COPD.

maTE: discovering expressed interactions between microRNAs and their targets

2019 ◽  
Vol 35 (20) ◽  
pp. 4020-4028 ◽  
Author(s):  
Malik Yousef ◽  
Loai Abdallah ◽  
Jens Allmer
Keyword(s):  
Gene Expression ◽  
Target Genes ◽  
Training Data ◽  
Supplementary Information ◽  
Protein Abundance ◽  
Expression Data ◽  
Mirna Regulation ◽  
Novel Approach ◽  
The Difference ◽  
And Control

Abstract Motivation Disease is often manifested via changes in transcript and protein abundance. MicroRNAs (miRNAs) are instrumental in regulating protein abundance and may measurably influence transcript levels. miRNAs often target more than one mRNA (for humans, the average is three), and mRNAs are often targeted by more than one miRNA (for the genes considered in this study, the average is also three). Therefore, it is difficult to determine the miRNAs that may cause the observed differential gene expression. We present a novel approach, maTE, which is based on machine learning, that integrates information about miRNA target genes with gene expression data. maTE depends on the availability of a sufficient amount of patient and control samples. The samples are used to train classifiers to accurately classify the samples on a per miRNA basis. Multiple high scoring miRNAs are used to build a final classifier to improve separation. Results The aim of the study is to find a set of miRNAs causing the regulation of their target genes that best explains the difference between groups (e.g. cancer versus control). maTE provides a list of significant groups of genes where each group is targeted by a specific miRNA. For the datasets used in this study, maTE generally achieves an accuracy well above 80%. Also, the results show that when the accuracy is much lower (e.g. ∼50%), the set of miRNAs provided is likely not causative of the difference in expression. This new approach of integrating miRNA regulation with expression data yields powerful results and is independent of external labels and training data. Thereby, this approach allows new avenues for exploring miRNA regulation and may enable the development of miRNA-based biomarkers and drugs. Availability and implementation The KNIME workflow, implementing maTE, is available at Bioinformatics online. Supplementary information Supplementary data are available at Bioinformatics online.

ROLE OF PHARMACIST INTERVENTION ON COPD PATIENTS OF SELECTED AREAS IN CHITRADURGA: A KAP STUDY

2019 ◽  
Vol 8 (2) ◽  
Author(s):  
Melvin K Mathews ◽  
Abubaker Siddiq ◽  
Bharathi D R
Keyword(s):  
Illness Perceptions ◽  
Pharmacist Intervention ◽  
Cross Sectional Study ◽  
Chronic Obstructive ◽  
Cross Sectional ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients ◽  
Post Test ◽  
Knowledge Practice ◽  
And Control

Background: Chronic obstructive pulmonary disease (COPD) is preventable and treatable disease state characterized by air flow limitation that is not fully reversible. Severity of the symptoms is increased during exacerbations. Objectives: The purpose of the study is to assess and improve the knowledge regarding COPD among study subjects. Materials and Methods: A Cross-sectional interventional study was carried out among the peoples in selected areas of the Chitradurga city for a period of six months. Result: A total 207 subjects enrolled in the study in that 155 male and 52 females. In our study mean score of post test was more (5.87±1.68) when compare to pre-test (2.63±1.46) which show significant increase in their knowledge after educating them (p=0.000). A total of 207 subjects were enrolled into the study. SPSS Software was used to calculate the statistical estimation. Paired t-test was used to detect the association status of different variables. Conclusion: The relatively good level of COPD awareness needs to be maintained to facilitate future prevention and control of the disease. This study had identified that negative illness perceptions should be targeted, so that they will not avoid patients from seeking for COPD treatment and adhere to it. Key words: Cross sectional study, Knowledge, practice, COPD.

scholarly journals Analysis of miRNAs Targeted Storage Regulatory Genes during Soybean Seed Development Based on Transcriptome Sequencing

Genes ◽  
2019 ◽  
Vol 10 (6) ◽  
pp. 408 ◽  
Author(s):  
Jing-Yao Yu ◽  
Zhan-Guo Zhang ◽  
Shi-Yu Huang ◽  
Xue Han ◽  
Xin-Yu Wang ◽  
...  
Keyword(s):  
Expression Pattern ◽  
Seed Development ◽  
Small Rna ◽  
Target Genes ◽  
Soybean Seed ◽  
Regulatory Genes ◽  
Small Rna Sequencing ◽  
Grain Development ◽  
Regulatory Relationship ◽  
Novel Mirna

Soybeans are an important cash crop and are widely used as a source of vegetable protein and edible oil. MicroRNAs (miRNA) are endogenous small RNA that play an important regulatory role in the evolutionarily conserved system of gene expression. In this study, we selected four lines with extreme phenotypes, as well as high or low protein and oil content, from the chromosome segment substitution line (CSSL) constructed from suinong (SN14) and ZYD00006, and planted and sampled at three stages of grain development for small RNA sequencing and expression analysis. The sequencing results revealed the expression pattern of miRNA in the materials, and predicted miRNA-targeted regulatory genes, including 1967 pairs of corresponding relationships between known-miRNA and their target genes, as well as 597 pairs of corresponding relationships between novel-miRNA and their target genes. After screening and annotating genes that were targeted for regulation, five specific genes were identified to be differentially expressed during seed development and subsequently analyzed for their regulatory relationship with miRNAs. The expression pattern of the targeted gene was verified by Real-time Quantitative PCR (RT-qPCR). Our research provides more information about the miRNA regulatory network in soybeans and further identifies useful genes that regulate storage during soy grain development, providing a theoretical basis for the regulation of soybean quality traits.

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