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 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.

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.

Comparison of miRNA Expression Profiles in Leukemia-Derived Microvesicles and Corresponding Leukemia Cells and Analysis of Their Roles in Leukemia

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1388-1388
Author(s):  
Xiaomei Chen ◽  
Fang Liu ◽  
Wei Xiong ◽  
Xiangjun Chen ◽  
Cong Lu ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Mirna Expression ◽  
Tumor Suppressors ◽  
Target Genes ◽  
Expression Profiles ◽  
K562 Cells ◽  
Cell Types ◽  
Leukemic Cells ◽  
Mirna Expression Profiles ◽  
Tumor Suppressor Mirnas

Abstract Abstract 1388 Microvesicles(MVs) are small exosomes of endocytic origin released by normal healthy or damaged cell types, including leukemic cells. MVs have been considered as cell dust, however, recent data bring evidences that MVs generated during cell activation or apoptosis can transfer biologic messages between different cell types. MicroRNAs (miRNAs) have been demonstrated to be aberrantly expressed in leukemia and the overall miRNA expression could differentiate normal versus leukemia. The MVs expressing miRNAs were found in the primary tumors. However it is currently unknown whether miRNA content changes in MVs derived from leukemic cells. Here we compared the miRNA expression in leukemia-derived MVs to corresponding leukemia cells and analysed their roles in leukemia. K562 cells were cultured and collected. MVs derived from K562 cells were also isolated. The presence and levels of specific miRNAs from both MVs derived from K562 cells and K562 cells were determined by Agilent miRNA microarray analysis probing for 888 miRNAs. Some selected miRNAs were verified by real time qRT-PCR. Bioinformatic software tools were used to predict the target genes of identified miRNAs and define their function. Our results showed that 77 and 122 miRNAs were only expressed in MVs and K562 cells, respectively. There were significant differences in miRNA expression profiles between MVs and K562 cells. We also found that 112 miRNAs were co-expressed in MVs and K562 cells. This observaton may suggest that compartmentalization of miRNAs from cells into to MVs, for at least some miRNAs, is an active (selective) process. Among those abnormally expressed miRNAs, some have been proposed oncomiRNAs or tumor suppressors. For example, miR-155, has been proposed as oncomiRNA, was abnormally expressed only in MVs in our study, suggesting that oncomiRNA was present in MVs. Further analysis revealed that 39 potential target genes regulated by miR-155. Among them, 4 genes involed in oncogenes and the signal genes. OncomiRNAs such as miR-27a and miR-21 expressed in both MVs and corresponding cells, indicating that MVs bear miRNA characteristic of the cell origin. MVs, released into the leukemia microenvironment, play an important role in leukemia. In contrast to oncomiRNAs, if miRNA is associated with tumor suppressive activity, it is regarded as a tumor suppressor (oncosuppressor). The aberrantly expressed miR-125a-3p, miR-125-5p,miR-27b, which have implicated as tumor suppressors, appear in both cellular and MVs of leukemia in our study. MiR-125a-3p, miR-125-5p and miR-27b regulated 308 potential target genes. To our knowledge, 10 of them are tumor suppression genes. It is possible that these aberrantly expressed tumor suppressor miRNAs decreased or lost their roles of tumor suppression, which led to decrease or loss their roles of regulating their target genes including oncogenes, consequently resulted in leukemia. Since K562 cells presented t(9;22), we further examined the predicted function of the 6 expressed miRNAs located in chrosome 9 (hsa-miR-188-5p,hsa-miR-602)and 22(hsa-let-7b,hsa-miR-1249,hsa-miR-130b,hsa-miR-185), which expressed both in the MVs and K562 cells. Using the TargetScan, we found 442 predicted targets regulated by 6 miRNAs. Those miRNAs may play roles in leukemia via these 422 genes. This study is the first to identify and define miRNA expression between K562 cells presented t(9;22), derived from K562 cells and their corresponding cells. We found significant differences in miRNA expression between MVs and corresponding leukemia. K562 cells released MVs riched in miRNAs including oncomiRNAs or tumor suppressor miRNAs into leukemia microenvironment, which play a role in leukemia via regulating their targer genes including oncogenes, consequently resulted in leukemia. Disclosures: No relevant conflicts of interest to declare.

Analysis of Microvesicle Microrna Expression Profiles and Their Functional Roles in ALL Subtypes

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1488-1488
Author(s):  
Xiaomei Chen ◽  
Wei Xiong ◽  
Xiangjun Chen ◽  
Cong Lu ◽  
Fang Liu ◽  
...  
Keyword(s):  
Cell Line ◽  
Mirna Expression ◽  
Target Genes ◽  
Expression Profiles ◽  
Jurkat Cells ◽  
Negative Regulator ◽  
Altered Expression ◽  
Normal Peripheral Blood ◽  
Potential Target ◽  
Mirna Expression Profiles

Abstract Abstract 1488 Microvesicles (MVs) released by leukemia cells constitute an important part of the leukemia microenvironment. As a cell-to-cell communication tool, MVs transfer microRNA(miRNA) between cells. MVs miRNAs may be valuable not only as a diagnostic tool but may also provide an insight in the role of miRNAs playing in the underlying of pathophysiologic processes of various leukemia. It is worth evaluating whether MVs possess some unique miRNA content depending on their corresponding leukemia origin that could be applicable in diagnosis. Hence, we determined the miRNA expression profiles of ALL-derived MVs using Agilent miRNA microarray analysis. The five miRNAs obtained by microarray profiling were validated using real-time PCR. The putative target genes were predicted by bioformation software. Here, we provided MVs miRNA patterns derived from the healthy controls, B-ALL cell line Nalm 6 cells and T-ALL cell line Jurkat cells. We identified 182 dysregulated miRNAs in MVs derived from Nalm 6 cells as compared with MVs from normal controls (P<0.05); both up regulated(123/182) and down regulated(59/182) expressions were observed. Likewise 166 miRNAs were significantly differentially expressed in MVs derived from Jurkat cells versus MVs from normal peripheral blood (P<0.05), 114 miRNAs of which (114/166) were up expression and 52 miRNAs (52/166) were down expression. We also fould that 44 miRNAs were only detected in B-ALL-derived MVs. MiR-1290, miR-1246, miR-1268, miR-1226, and miR-424 were top 5 expressed in Nalm 6 derived MVs, suggesting that those miRNAs may play an important role in B-ALL. We observed that 16 miRNAs detected only in T cell derived MVs. MiR-96 is up regulated in MVs from T-ALL cells but not expressed in B-ALL. Specific and functional target sites for miR-96, exist in the 3'-UTR of the miRNA that encodes the putative tumor suppressor transcription factor FOXO1. The expression signatures of miR-96 could discriminate B-ALL from T-ALL. In contrast, the MVs from B-ALL cell line, shared 100 miRNAs with MVs from T-ALL cell line, suggestting that those miRNAs play roles in both B-and T-ALL. Of 100 miRNAs, 99 miRNAs were high expression, indicating that miRNAs were active in ALL. This obsearvation suggusted that miRNA differential expression in MVs were partially significantly related to subtypes of acute lymphoblastic leukemia. Intriguing is that miR1290 is top higher expression both in MVs derived from Nalm6 cells and from Jurkat cells; miR-1290 is 475-fold higher expressed in Nalm 6 derived MVs versus MVs from normal cells, whereas this miRNA is 245-fold higher expressed in Jurkat cells. Five of these miRNAs were selected to be further assayed and validated by PCR. The qRT-PCR results correlated well with the microarray data. In addition, we found seven miRNAs(miR-148b, miR-484, miR-let-7f, let-7a, miR-223, miR16 and miR-27b) were located near the 11q23 chromosomal region. With bioinformatic tools (TargetScan), we predicted potential target genes for those miRNAs that exhibited altered expression in MVs from B-ALL and T-ALL. The p85 subunit of phosphatidylinositol 3-kinase (PI3-K) was found to be a potential target of miR-320. Of particular interest, we found that protein tyrosine phosphatase-like member b (PTPLB) may be a potential target of miR-1290. The 474-fold increase in miR-1290 in MVs from Nalm 6 cells, indicating that miR-1290 may participate in the modulation of leukemia by targeting PTPLB, a specific, negative regulator of p210 bcr-abl signal. In conclusion, we identified miRNAs and found that miRNA expression profiles were ALL subtype-specific. Altered miRNA expression levels may lead to an inappropriate expression of target oncoproteins or target tumor suppressors, thereby facilitating the development of leukemia. These findings expanded the potential diagnostic markers of leukemia and provided useful information to ALL pathogenesis. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Ewing’s Sarcoma: An Analysis of miRNA Expression Profiles and Target Genes in Paraffin-Embedded Primary Tumor Tissue

2016 ◽  
Vol 17 (5) ◽  
pp. 656 ◽  
Author(s):  
Antonina Parafioriti ◽  
Caterina Bason ◽  
Elisabetta Armiraglio ◽  
Lucia Calciano ◽  
Primo Daolio ◽  
...  
Keyword(s):  
Mirna Expression ◽  
Primary Tumor ◽  
Target Genes ◽  
Tumor Tissue ◽  
Ewing’S Sarcoma ◽  
Ewing's Sarcoma ◽  
Expression Profiles ◽  
Mirna Expression Profiles

scholarly journals Differential miRNA Profiles Correlate With Disparate Immunity Outcomes Associated With Vaccine Immunization and Chlamydial Infection

2021 ◽  
Vol 12 ◽  
Author(s):  
Simone Howard ◽  
Shakyra Richardson ◽  
Ifeyinwa Benyeogor ◽  
Yusuf Omosun ◽  
Kamran Dye ◽  
...  
Keyword(s):  
Immune Responses ◽  
Mirna Expression ◽  
Clustering Analysis ◽  
Chlamydial Infection ◽  
Target Genes ◽  
Expression Profiles ◽  
Biological Processes ◽  
Dc Vaccine ◽  
Mirna Expression Profiles ◽  
Experimental Group

Vaccine-induced immune responses following immunization with promising Chlamydia vaccines protected experimental animals from Chlamydia-induced upper genital tract pathologies and infertility. In contrast, primary genital infection with live Chlamydia does not protect against these pathologies. We hypothesized that differential miRNA profiles induced in the upper genital tracts (UGT) of mice correlate with the disparate immunity vs. pathologic outcomes associated with vaccine immunization and chlamydial infection. Thus, miRNA expression profiles in the UGT of mice after Chlamydia infection (Live EB) and immunization with dendritic cell (DC)-based vaccine (DC vaccine) or VCG-based vaccine (VCG vaccine) were compared using the NanoString nCounter Mouse miRNA assay. Of the 602 miRNAs differentially expressed (DE) in the UGT of immunized and infected mice, we selected 58 with counts &gt;100 and p-values &lt; 0.05 for further analysis. Interestingly, vaccine immunization and Chlamydia infection induced the expression of distinct miRNA profiles with a higher proportion in vaccine-immunized compared to Chlamydia infected mice; DC vaccine (41), VCG vaccine (23), and Live EB (15). Hierarchical clustering analysis showed notable differences in the uniquely DE miRNAs for each experimental group, with DC vaccine showing the highest number (21 up-regulated, five down-regulated), VCG vaccine (two up-regulated, five down-regulated), and live EB (two up-regulated, four down-regulated). The DC vaccine-immunized group showed the highest number (21 up-regulated and five down-regulated compared to two up-regulated and four down-regulated in the live Chlamydia infected group). Pathway analysis showed that the DE miRNAs target genes that regulate several biological processes and functions associated with immune response and inflammation. These results suggest that the induction of differential miRNA expression plays a significant role in the disparate immunity outcomes associated with Chlamydia infection and vaccination.

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.

Sign in / Sign up

Export Citation Format

Share Document