Persistent gene expression in mouse vagina exposed neonatally to diethylstilbestrol

Developmental exposure to a synthetic estrogen, diethylstilbestrol (DES), induces carcinogenesis in human and laboratory animals. In mice, neonatal DES treatment induces persistent proliferation and keratinization of the vaginal epithelium, even in the absence of the ovaries, resulting in cancerous lesions later in life. To understand the mechanisms underlying this persistent cell proliferation and differentiation, we characterized the gene expression patterns in the neonatally DES-exposed mouse vagina using DNA microarray and real-time quantitative RT-PCR. We found that genes related to cellular signaling, which are candidates for mediating the persistent proliferation and differentiation, were altered, and genes related to the immune system were decreased in the neonatally DES-exposed mouse vagina. We also noted high expression of interleukin-1 (IL-1)-related genes accompanied by phosphorylation of JNK1. In addition, expression IGF-I and its binding proteins was modulated and led to phosphorylation of IGF-I receptor and Akt, which is one of the downstream factors of IGF-I signaling. This led us to characterize the expression as well as the phosphorylation status of IL-1 and IGF-I signaling pathway components which may activate the phosphorylation cascade in the vagina of mice exposed neonatally to DES. These findings give insight into persistent activation in the vagina of mice exposed neonatally to DES.

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A Novel Method for Predicting Disease-Associated LncRNA-MiRNA Pairs Based on the Higher-Order Orthogonal Iteration

Computational and Mathematical Methods in Medicine ◽

10.1155/2019/7614850 ◽

2019 ◽

Vol 2019 ◽

pp. 1-13 ◽

Cited By ~ 2

Author(s):

Zhanwei Xuan ◽

Xiang Feng ◽

Jingwen Yu ◽

Pengyao Ping ◽

Haochen Zhao ◽

...

Keyword(s):

Higher Order ◽

System Level ◽

Cell Proliferation And Differentiation ◽

Proliferation And Differentiation ◽

Great Insight ◽

Novel Method ◽

Global And Local ◽

Novel Model ◽

Insight Into ◽

Orthogonal Iteration

A lot of research studies have shown that many complex human diseases are associated not only with microRNAs (miRNAs) but also with long noncoding RNAs (lncRNAs). However, most of the current existing studies focus on the prediction of disease-related miRNAs or lncRNAs, and to our knowledge, until now, there are few literature studies reported to pay attention to the study of impact of miRNA-lncRNA pairs on diseases, although more and more studies have shown that both lncRNAs and miRNAs play important roles in cell proliferation and differentiation during the recent years. The identification of disease-related genes provides great insight into the underlying pathogenesis of diseases at a system level. In this study, a novel model called PADLMHOOI was proposed to predict potential associations between diseases and lncRNA-miRNA pairs based on the higher-order orthogonal iteration, and in order to evaluate its prediction performance, the global and local LOOCV were implemented, respectively, and simulation results demonstrated that PADLMHOOI could achieve reliable AUCs of 0.9545 and 0.8874 in global and local LOOCV separately. Moreover, case studies further demonstrated the effectiveness of PADLMHOOI to infer unknown disease-related lncRNA-miRNA pairs.

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Influence of somatotropin on lipid metabolism and IGF gene expression in porcine adipose tissue

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1992.263.4.e637 ◽

1992 ◽

Vol 263 (4) ◽

pp. E637-E645 ◽

Cited By ~ 1

Author(s):

C. K. Wolverton ◽

M. J. Azain ◽

J. Y. Duffy ◽

M. E. White ◽

T. G. Ramsay

Keyword(s):

Gene Expression ◽

Adipose Tissue ◽

Dietary Fat ◽

Subcutaneous Adipose Tissue ◽

Proliferation And Differentiation ◽

Igf I ◽

Systemic Factors ◽

Subcutaneous Adipose ◽

Acid Esterification

The present study was designed to evaluate the effects of porcine somatotropin (pST) treatment (2 mg/day) and dietary fat (10%) separately and in combination on the metabolic activity of subcutaneous adipose tissue, serum adipogenic activity, and insulin-like growth factor (IGF) gene expression within adipose tissue from growing 5- to 6-mo-old barrows. This study attempted to determine how these factors might contribute to the reported changes in adiposity of treated swine. Biopsies of adipose tissue were collected after 28 days of treatment following anesthesia with thiopental sodium (15 mg/kg iv). Somatotropin inhibited in vitro glucose oxidation and lipogenesis in adipose tissue but did not affect fatty acid esterification. Adipogenic activity of serum was not altered by pST treatment. Subcutaneous adipose tissue contained mRNA for IGF-I and -II, and pST administration increased the abundance of IGF-I mRNA. Dietary fat had no effect on these variables. Thus somatotropin reduces glucose metabolism in porcine subcutaneous adipose tissue. Preadipocyte proliferation and differentiation are not affected by somatotropin through its actions on systemic factors. Dietary fat provides no additional benefit in combination with pST administration to affect accretion of adipose tissue in growing swine.

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The influence of direct and indirect fibroblast cell contact on human myogenic cell behavior and gene expression in vitro

Journal of Applied Physiology ◽

10.1152/japplphysiol.00215.2019 ◽

2019 ◽

Vol 127 (2) ◽

pp. 342-355 ◽

Cited By ~ 1

Author(s):

Cecilie J. L. Bechshøft ◽

Peter Schjerling ◽

Michael Kjaer ◽

Abigail L. Mackey

Keyword(s):

Gene Expression ◽

Skeletal Muscle ◽

Cell Proliferation ◽

Myogenic Cell ◽

Mrna Levels ◽

Indirect Contact ◽

Permeable Membrane ◽

Primary Myoblasts ◽

Cell Proliferation And Differentiation ◽

Proliferation And Differentiation

Underpinning skeletal muscle plasticity is the interplay between many cell types, of which fibroblasts are emerging as potent players, both negatively in the development of fibrosis but also positively in stimulating muscle repair through enhancing myogenesis. The mechanisms behind this interaction however remain unknown. To investigate this, waste hamstring muscle tissue was obtained from eight healthy young men undergoing reconstructive anterior cruciate ligament surgery and primary myoblasts and fibroblasts were isolated. Myoblasts were cultured alone or with fibroblasts, either in direct or indirect contact (separated by an insert with a permeable membrane). The myogenesis parameters proliferation, differentiation, and fusion were determined from immunostained cells, while, in replicate samples, gene expression levels of GAPDH, Ki67, Pax7, MyoD, myogenin, myomaker, MHC-Iβ, TCF7L2, COL1A1, and p16 were determined by RT-PCR. We found only trends for an influence of skeletal muscle fibroblasts on myogenic cell proliferation and differentiation. While greater mRNA levels of GAPDH, Pax7, MyoD, myogenin, and MHC-Iβ were observed in myogenic cells in indirect contact with fibroblasts (insert) when compared with cells cultured alone, a similar effect of an empty insert was also observed. In conclusion we find very little influence of skeletal muscle fibroblasts on myoblasts derived from the same tissue, although it cannot be excluded that a different outcome would be seen under less optimal myogenic growth conditions. NEW & NOTEWORTHY Using passage one primary myoblasts and fibroblasts isolated from human skeletal muscle, we found only a trend for an effect of skeletal muscle fibroblasts on myogenic cell proliferation and differentiation. This is contrary to previous reports and raises the possibility that fibroblasts of different tissue origins exert distinct roles.

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Expression of Inflammation-Related Genes Is Altered in Gastric Tissue of Patients with Advanced Stages of NAFLD

Mediators of Inflammation ◽

10.1155/2013/684237 ◽

2013 ◽

Vol 2013 ◽

pp. 1-10 ◽

Cited By ~ 5

Author(s):

Rohini Mehta ◽

Aybike Birerdinc ◽

Arpan Neupane ◽

Amirhossein Shamsaddini ◽

Arian Afendy ◽

...

Keyword(s):

Gene Expression ◽

Hepatic Fibrosis ◽

Interleukin 1 ◽

Expression Patterns ◽

Interleukin 8 ◽

Morbidly Obese ◽

Low Grade ◽

Mrna Levels ◽

Gastric Tissue ◽

Hepatic Inflammation

Obesity is associated with chronic low-grade inflammation perpetuated by visceral adipose. Other organs, particularly stomach and intestine, may also overproduce proinflammatory molecules. We examined the gene expression patterns in gastric tissue of morbidly obese patients with nonalcoholic fatty liver disease (NAFLD) and compared the changes in gene expression in different histological forms of NAFLD. Stomach tissue samples from 20 morbidly obese NAFLD patients who were undergoing sleeve gastrectomy were profiled using qPCR for 84 genes encoding inflammatory cytokines, chemokines, their receptors, and other components of inflammatory cascades. Interleukin 8 receptor-beta (IL8RB) gene overexpression in gastric tissue was correlated with the presence of hepatic steatosis, hepatic fibrosis, and histologic diagnosis of nonalcoholic steatohepatitis (NASH). Expression levels of soluble interleukin 1 receptor antagonist (IL1RN) were correlated with the presence of NASH and hepatic fibrosis. mRNA levels of interleukin 8 (IL8), chemokine (C-C motif) ligand 4 (CCL4), and its receptor chemokine (C-C motif) receptor type 5 (CCR5) showed a significant increase in patients with advanced hepatic inflammation and were correlated with the severity of the hepatic inflammation. The results of our study suggest that changes in expression patterns for inflammatory molecule encoding genes within gastric tissue may contribute to the pathogenesis of obesity-related NAFLD.

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Autoregulation Is Essential for Precise Temporal and Steady-State Regulation by the Bordetella BvgAS Phosphorelay

Journal of Bacteriology ◽

10.1128/jb.01684-06 ◽

2006 ◽

Vol 189 (5) ◽

pp. 1974-1982 ◽

Cited By ~ 26

Author(s):

Corinne L. Williams ◽

Peggy A. Cotter

Keyword(s):

Gene Expression ◽

Steady State ◽

Response Regulator ◽

Expression Patterns ◽

State Regulation ◽

Temporal Expression ◽

Multiple Gene ◽

Insight Into

ABSTRACT The Bordetella BvgAS virulence control system is prototypical of phosphorelays that use a polydomain sensor and a response regulator to control gene expression in response to environmental cues. BvgAS controls the expression of at least three distinct phenotypic phases (Bvg−, Bvgi, and Bvg+) by differentially regulating the expression of at least four classes of genes. Among the loci regulated by BvgAS is bvgAS itself. We investigated the role of autoregulation in the ability of BvgAS to control multiple gene expression patterns in a temporal and steady-state manner by constructing Bordetella bronchiseptica strains in which the bvgAS promoter was replaced with constitutively active promoters. Our results show that positive autoregulation of bvgAS transcription is required for the temporal expression of multiple phenotypic phases that occurs in response to a shift from Bvg−-phase conditions to Bvg+-phase conditions. Autoregulation was also shown to contribute to steady-state regulation; it influences the sensitivity of the system in response to subtle differences in signal intensity. In addition, considered in relation to BvgA and BvgS activities demonstrated in vitro, our results provide insight into how BvgA and BvgS function mechanistically.

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Regulation of spatial and temporal gene expression in an animal germline

10.1101/348425 ◽

2018 ◽

Cited By ~ 1

Author(s):

Asija Diag ◽

Marcel Schilling ◽

Filippos Klironomos ◽

Salah Ayoub ◽

Nikolaus Rajewsky

Keyword(s):

Gene Expression ◽

Regulatory Mechanisms ◽

Rna Expression ◽

Temporal Expression ◽

Temporal Gene Expression ◽

Cell Proliferation And Differentiation ◽

Proliferation And Differentiation ◽

Gene Regulatory ◽

Spatio Temporal

SUMMARYIn animal germlines, regulation of cell proliferation and differentiation is particularly important but poorly understood. Here, using a cryo-cut approach, we mapped RNA expression along the Caenorhabditis elegans germline and, using mutants, dissected gene regulatory mechanisms that control spatio-temporal expression. We detected, at near single-cell resolution, > 10,000 mRNAs, > 300 miRNAs and numerous novel miRNAs. Most RNAs were organized in distinct spatial patterns. Germline-specific miRNAs and their targets were co-localized. Moreover, we observed differential 3’ UTR isoform usage for hundreds of mRNAs. In tumorous gld-2 gld-1 mutants, gene expression was strongly perturbed. In particular, differential 3’ UTR usage was significantly impaired. We propose that PIE-1, a transcriptional repressor, functions to maintain spatial gene expression. Our data also suggest that cpsf-4 and fipp-1 control differential 3’ UTR usage for hundreds of genes. Finally, we constructed a “virtual gonad” enabling “virtual in situ hybridizations” and access to all data (https://shiny.mdc-berlin.de/spacegerm/).

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Dysregulation of ANKRD11 Influenced Hematopoisis By Histone Acetylation-Mediated Gene Expression in Myelodysplastic Syndrome

Blood ◽

10.1182/blood.v128.22.4292.4292 ◽

2016 ◽

Vol 128 (22) ◽

pp. 4292-4292

Author(s):

Youshan Zhao ◽

Feng Xu ◽

Juan Guo ◽

Sida Zhao ◽

Chunkang Chang ◽

...

Keyword(s):

Gene Expression ◽

Cell Proliferation ◽

Histone Acetylation ◽

Mrna Expression ◽

Cell Line ◽

Expression Levels ◽

Target Sequencing ◽

Cell Proliferation And Differentiation ◽

Proliferation And Differentiation ◽

Mrna Expression Levels

Abstract Background and Object In addition to histone deacetylation, the importance of histone over-acetylation induced oncogene transcription in initiation and progression of myelodysplastic syndrome (MDS) has been proposed recently. Our previous whole-exome sequencing identified a new somatic mutation, ANKRD11, an important factor in histone acetylation regulation. Its roles in MDS pathophysiology need to be clarified. Methods The next generation target sequencing (Including ANKRD11) was carried out in 320 patients with MDS using the MiSeq Benchtop Sequencer. ANKRD11 mRNA expression in bone marrow of MDS was measured by real-time PCR. Loss and gain of function assay were carried out in myeloid cell lines K562, MEG-01£¬or SKM-1 to observe the influence on cell proliferation and differentiation . The levels of histone acetylation at H3 and H4 were detected by Western blot. Results Target sequencing in a cohort of 320 MDS patients identified 14 of ANKRD11 mutations (4.38%, Fig.1), which were confirmed by Sanger sequencing. Meanwhile, no ANKRD11 mutations in 100 normal controls were defined. ANKRD11 mutations occurred frequently in exons 10 and 9. The mRNA expression levels of ANKRD11 were significantly decreased in MDS patients, especially in ANKRD11mutant patients (Fig.2). ANKRD11 knockdown in K562 and MEG-1 resulted in growth inhibition, cell cycle arrest and erythroid/megakaryocytic differentiation retardant. In MDS cell line SKM-1, the arrested differentiation was rescued by over-expression of ANKRD11. Consistent with a role for ANKRD11 in histone acetylation, ANKRD11 KD increased acetylation of histones H3 and H4 at H3K14 and H4K5 and resulted in the upregulation of genes involved in differentiation inhibilation (SOX6, P21, et al). Finally, the ANKRD11 KD-mediated influence on cell proliferation and differentiation were reversed by inhibiting histone acetyltransferase activity. Conclusion Our assay defined that ANKRD11 was a crucial chromatin regulator that suppress histone acetylation and then decrease gene expression during myeloid differentiation, providing a likely explanation for its role in MDS pathogenesis. This study further support histone acetylase inhibitor as a potential treatment in MDS. Figure ANKRD11mutation distribution (a) and coexist with other mutations (b). Figure. ANKRD11mutation distribution (a) and coexist with other mutations (b). Figure The mRNA expression levels of ANKRD11in our MDS (A, C) subset and GEO data (B). Figure. The mRNA expression levels of ANKRD11in our MDS (A, C) subset and GEO data (B). Changes of histone acetylation in ANKRD11-KD cell line (MEG-01). ANKRD11 KD significantly increased acetylation of histones H3 and H4 at H3K14 and H4K5. Changes of histone acetylation in ANKRD11-KD cell line (MEG-01). ANKRD11 KD significantly increased acetylation of histones H3 and H4 at H3K14 and H4K5. Disclosures No relevant conflicts of interest to declare.

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Genome edited colorectal cancer organoid models reveal distinct microRNA activity patterns across different mutation profiles

10.1101/2021.12.13.472432 ◽

2021 ◽

Author(s):

Jonathan W Villanueva ◽

Lawrence Kwong ◽

Teng Han ◽

Salvador Alonso Martinez ◽

Fong Cheng Pan ◽

...

Keyword(s):

Gene Expression ◽

Colorectal Cancer ◽

Genetically Modified ◽

Activity Patterns ◽

Expression Patterns ◽

Regulatory Mechanisms ◽

Oncogenic Mutations ◽

Gene Regulatory ◽

Insight Into

Somatic mutations drive colorectal cancer (CRC) by disrupting gene regulatory mechanisms. Distinct combinations of mutations can result in unique changes to regulatory mechanisms leading to variability in the efficacy of therapeutics. MicroRNAs are important regulators of gene expression, and their activity can be altered by oncogenic mutations. However, it is unknown how distinct combinations of CRC-risk mutations differentially affect microRNAs. Here, using genetically-modified mouse intestinal organoid (enteroid) models, we identify ten different modules of microRNA expression patterns across distinct combinations of mutations common in CRC. We also show that miR-24-3p, which is aberrant in genetically-modified mouse enteroids and human colonoids irrespective of mutational context, is a master regulator of gene expression in CRC. In follow-up experiments, we also demonstrate that miR-24 promotes CRC cell survival. These findings offer insight into the mechanisms that drive inter-tumor heterogeneity and highlight candidate microRNA therapeutic targets for the advancement of precision medicine for CRC.

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Functional analyses of miRNA-146b-5p during myogenic proliferation and differentiation in chicken myoblasts

10.21203/rs.2.18746/v2 ◽

2020 ◽

Author(s):

Jeong Hyo Lee ◽

Seo Woo Kim ◽

Ji Seon Han ◽

Seung Pyo Shin ◽

Sang In Lee ◽

...

Keyword(s):

Gene Expression ◽

Muscle Development ◽

Expression Patterns ◽

Global Gene Expression ◽

Economic Traits ◽

Gene Sets ◽

Proliferation And Differentiation ◽

Genomic Studies ◽

Myoblast Cells ◽

Functional Analyses

Abstract Background: In the poultry and livestock industries, precise genetic information is crucial for improving economic traits. Thus, functional genomic studies help to generate faster, healthier, and more efficient animal production. Chicken myoblast cells, which are required for muscle development and regeneration, are particularly important because chicken growth is closely related to muscle mass. Results: In this study, we induced expression of microRNA-146b-5p mediated by the piggyBac transposon system in primary chicken myoblast (pCM) cells. Subsequently, we analyzed and compared the proliferation and differentiation capacity and also examined the expression of related genes in regular pCM (rpCM) cells and pCM cells overexpressing miRNA-146b-5p (pCM-146b OE cells). pCM-146b OE cells showed increased proliferation and upregulated gene expression related to cell proliferation. In addition, next-generation sequencing analyses were performed to compare global gene expression patterns between rpCM cells and pCM-146b OE cells. We found that the higher proliferation in pCM-146b OE cells was the result of upregulation of gene sets related to the cell cycle. Moreover, miRNA-146b-5p overexpression had inhibitory effects on myotube differentiation in pCM cells. Conclusions: Collectively these results demonstrate that miR-146b-5p is closely related to the proliferation and differentiation of chicken myogenic cells as a modulator of post-transcription.

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NF-κB signaling dynamics is controlled by a dose-sensing autoregulatory loop

Science Signaling ◽

10.1126/scisignal.aau3568 ◽

2019 ◽

Vol 12 (579) ◽

pp. eaau3568 ◽

Cited By ~ 11

Author(s):

Mialy M. DeFelice ◽

Helen R. Clark ◽

Jacob J. Hughey ◽

Inbal Maayan ◽

Takamasa Kudo ◽

...

Keyword(s):

Gene Expression ◽

Single Cell Analysis ◽

Interleukin 1 ◽

Expression Patterns ◽

Critical Role ◽

Signal Propagation ◽

Innate Immune ◽

Signaling Dynamics ◽

Molecular Events ◽

Dose Dependent

Over the last decade, multiple studies have shown that signaling proteins activated in different temporal patterns, such as oscillatory, transient, and sustained, can result in distinct gene expression patterns or cell fates. However, the molecular events that ensure appropriate stimulus- and dose-dependent dynamics are not often understood and are difficult to investigate. Here, we used single-cell analysis to dissect the mechanisms underlying the stimulus- and dose-encoding patterns in the innate immune signaling network. We found that Toll-like receptor (TLR) and interleukin-1 receptor (IL-1R) signaling dynamics relied on a dose-dependent, autoinhibitory loop that rendered cells refractory to further stimulation. Using inducible gene expression and optogenetics to perturb the network at different levels, we identified IL-1R–associated kinase 1 (IRAK1) as the dose-sensing node responsible for limiting signal flow during the innate immune response. Although the kinase activity of IRAK1 was not required for signal propagation, it played a critical role in inhibiting the nucleocytoplasmic oscillations of the transcription factor NF-κB. Thus, protein activities that may be “dispensable” from a topological perspective can nevertheless be essential in shaping the dynamic response to the external environment.

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