scholarly journals Computational Model for Predicting the Relationship Between Micro-RNAs and Their Target Messenger RNAs in Breast and Colon Cancers

2018 ◽  
Vol 17 ◽  
pp. 117693511878514
Author(s):  
Shinuk Kim
Keyword(s):  
Breast Cancer ◽  
Colon Cancer ◽  
Target Gene ◽  
Target Genes ◽  
Computational Method ◽  
Numerical Code ◽  
Messenger Rnas ◽  
Unknown Parameters ◽  
Micro Rnas ◽  
The Relationship

Motivation: Uncovering the relationship between micro-RNAs (miRNAs) and their target messenger RNAs (mRNAs) can provide critical information regarding the mechanisms underlying certain types of cancers. In this context, we have proposed a computational method, referred to as prediction analysis by optimization method (PAOM), to predict miRNA-mRNA relations using data from normal and cancer tissues, and then applying the relevant algorithms to colon and breast cancers. Specifically, we used 26 miRNAs and 26 mRNAs with 676 (= 26 × 26) relationships to be recovered as unknown parameters. Results: Optimization methods were used to detect 61 relationships in breast cancer and 32 relationships in colon cancer. Using sequence filtering, we detected 18 relationships in breast cancer and 15 relationships in colon cancer. Among the 18 relationships, CD24 is the target gene of let-7a and miR-98, and E2F1 is the target gene of miR-20. In addition, the frequencies of the target genes of miR-223, miR-23a, and miR-20 were significant in breast cancer, and the frequencies of the target genes of miR-17, miR-124, and miR-30a were found to be significant in colon cancer. Availability: The numerical code is available from the authors on request.

scholarly journals Micro RNAs in Regulation of Cellular Redox Homeostasis

2021 ◽  
Vol 22 (11) ◽  
pp. 6022
Author(s):  
Sylwia Ciesielska ◽  
Izabella Slezak-Prochazka ◽  
Patryk Bil ◽  
Joanna Rzeszowska-Wolny
Keyword(s):  
Target Genes ◽  
Redox Homeostasis ◽  
Messenger Rnas ◽  
Cellular Redox ◽  
Cell Responses ◽  
Regulatory Circuits ◽  
Micro Rnas ◽  
Cellular Behaviors ◽  
Homeostasis Regulation ◽  
Thioredoxin Reductases

In living cells Reactive Oxygen Species (ROS) participate in intra- and inter-cellular signaling and all cells contain specific systems that guard redox homeostasis. These systems contain both enzymes which may produce ROS such as NADPH-dependent and other oxidases or nitric oxide synthases, and ROS-neutralizing enzymes such as catalase, peroxiredoxins, thioredoxins, thioredoxin reductases, glutathione reductases, and many others. Most of the genes coding for these enzymes contain sequences targeted by micro RNAs (miRNAs), which are components of RNA-induced silencing complexes and play important roles in inhibiting translation of their targeted messenger RNAs (mRNAs). In this review we describe miRNAs that directly target and can influence enzymes responsible for scavenging of ROS and their possible role in cellular redox homeostasis. Regulation of antioxidant enzymes aims to adjust cells to survive in unstable oxidative environments; however, sometimes seemingly paradoxical phenomena appear where oxidative stress induces an increase in the levels of miRNAs which target genes which are supposed to neutralize ROS and therefore would be expected to decrease antioxidant levels. Here we show examples of such cellular behaviors and discuss the possible roles of miRNAs in redox regulatory circuits and further cell responses to stress.

scholarly journals MiR-940 promotes malignant progression of breast cancer by regulating FOXO3

2020 ◽  
Vol 40 (9) ◽  
Author(s):  
Huayao Zhang ◽  
Jingwen Peng ◽  
Jianguo Lai ◽  
Haiping Liu ◽  
Zhiyuan Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Colony Formation ◽  
Target Gene ◽  
Luciferase Reporter Assay ◽  
Luciferase Reporter ◽  
Reporter Assay ◽  
Poor Survival ◽  
High Level ◽  
The Relationship ◽  
Proliferation And Invasion

Abstract Breast cancer (BC) is a common cancer with poor survival. The present study aimed to explore the effect of miR-940 on the process of BC cells and its target gene FOXO3. The expression of miR-940 was assessed in BC tissues and cells using qRT-PCR. Furthermore, the correlation between miR-940 and prognosis of BC patients from the TCGA database was analyzed. CCK8 assays and colony formation assays were used to explore the effect of miR-940 on BC cell proliferation. The invasion abilities were detected by transwell assays. Luciferase reporter assay was performed to scrutinize the relationship between miR-940 and FOXO3. Finally, rescue experiments were performed through FOXO3 down-regulation and miR-940 inhibitors by using CCK8 assays, colony formation assays and transwell assays. miR-940 was significantly up-regulated in BC cells and tissues. In addition, the high level of miR-940 correlated with poor survival of BC patients (P=0.023). CCK8 assays, colony formation assays and transwell assays indicated that miR-940 promoted the proliferation and invasion abilities of BC cells. The luciferase reporter assay suggested that miR-940 directly targeted FOXO3. Moreover, we found that the effect of si-FOXO3 was rescued by miR-940 inhibitors in BC cells. miR-940 may promote the proliferation and invasion abilities of BC cells by targeting FOXO3. Our study suggested that miR-940 could be a novel molecular target for therapies against BC.

scholarly journals Using Context-Sensitive Text Mining to Identify miRNAs in Different Stages of Atherosclerosis

2019 ◽  
Vol 119 (08) ◽  
pp. 1247-1264 ◽  
Author(s):  
Markus Joppich ◽  
Christian Weber ◽  
Ralf Zimmer
Keyword(s):  
Data Analysis ◽  
Text Mining ◽  
High Throughput ◽  
Target Genes ◽  
Mirna Gene ◽  
Cell Types ◽  
Gene Interactions ◽  
Messenger Rnas ◽  
New Findings ◽  
Micro Rnas

790 human and mouse micro-RNAs (miRNAs) are involved in diseases. More than 26,428 miRNA–gene interactions are annotated in humans and mice. Most of these interactions are posttranscriptional regulations: miRNAs bind to the messenger RNAs (mRNAs) of genes and induce their degradation, thereby reducing the gene expression of target genes. For atherosclerosis, 667 miRNA–gene interactions for 124 miRNAs and 343 genes have been identified and described in numerous publications. Some interactions were observed through high-throughput experiments, others were predicted using bioinformatic methods, and some were determined by targeted experiments. Several reviews collect knowledge on miRNA–gene interactions in (specific aspects of) atherosclerosis.Here, we use our bioinformatics resource (atheMir) to give an overview of miRNA–gene interactions in the context of atherosclerosis. The interactions are based on public databases and context-based text mining of 28 million PubMed abstracts. The miRNA–gene interactions are obtained from more than 10,000 publications, of which more than 1,000 are in a cardiovascular disease context (266 in atherosclerosis). We discuss interesting miRNA–gene interactions in atherosclerosis, grouped by specific processes in different cell types and six phases of atherosclerotic progression. All evidence is referenced and easily accessible: Relevant interactions are provided by atheMir as supplementary tables for further evaluation and, for example, for the subsequent data analysis of high-throughput measurements as well as for the generation and validation of hypotheses. The atheMir approach has several advantages: (1) the evidence is easily accessible, (2) regulatory interactions are uniformly available for subsequent high-throughput data analysis, and (3) the resource can incrementally be updated with new findings.

scholarly journals In silico Analysis of Combinatorial microRNA Activity Reveals Target Genes and Pathways Associated with Breast Cancer Metastasis

2011 ◽  
Vol 10 ◽  
pp. CIN.S6631 ◽  
Author(s):  
Alan A. Dombkowski ◽  
Zakia Sultana ◽  
Douglas B. Craig ◽  
Hasan Jamil
Keyword(s):  
Breast Cancer ◽  
Cancer Metastasis ◽  
Target Genes ◽  
In Silico Analysis ◽  
Metastatic Potential ◽  
Breast Cancer Metastasis ◽  
Computational Method ◽  
Cytoskeleton Organization ◽  
Cellular Processes ◽  
Therapeutic Development

Aberrant microRNA activity has been reported in many diseases, and studies often find numerous microRNAs concurrently dysregulated. Most target genes have binding sites for multiple microRNAs, and mounting evidence indicates that it is important to consider their combinatorial effect on target gene repression. A recent study associated the coincident loss of expression of six microRNAs with metastatic potential in breast cancer. Here, we used a new computational method, miR-AT!, to investigate combinatorial activity among this group of microRNAs. We found that the set of transcripts having multiple target sites for these microRNAs was significantly enriched with genes involved in cellular processes commonly perturbed in metastatic tumors: cell cycle regulation, cytoskeleton organization, and cell adhesion. Network analysis revealed numerous target genes upstream of cyclin D1 and c-Myc, indicating that the collective loss of the six microRNAs may have a focal effect on these two key regulatory nodes. A number of genes previously implicated in cancer metastasis are among the predicted combinatorial targets, including TGFB1, ARPC3, and RANKL. In summary, our analysis reveals extensive combinatorial interactions that have notable implications for their potential role in breast cancer metastasis and in therapeutic development.

scholarly journals Genetic Evidence for a Protein Kinase A/Cubitus Interruptus Complex That Facilitates Processing of Cubitus Interruptus in Drosophila

Genetics ◽  
2001 ◽  
Vol 158 (3) ◽  
pp. 1157-1166
Author(s):  
John A Kiger ◽  
Cristin O'Shea
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Target Gene ◽  
Target Genes ◽  
Signal Transduction Pathway ◽  
Transduction Pathway ◽  
Cubitus Interruptus ◽  
Mutant Forms ◽  
The Relationship ◽  
Kinase A

Abstract Hedgehog (Hh) activates a signal transduction pathway regulating Cubitus interruptus (Ci). In the absence of Hh, full-length Ci (Ci-155) is bound in a complex that includes Costal2 (Cos2) and Fused (Fu). Ci-155 is phosphorylated by protein kinase A (PKA), inducing proteolysis to Ci-75, a transcriptional repressor. Hh signaling blocks proteolysis and produces an activated Ci-155 transcriptional activator. The relationship between PKA and the Ci/Cos2/Fu complex is unclear. Here we examine Hh target gene expression caused by mutant forms of PKA regulatory (PKAr) and catalytic (PKAc) subunits and by the PKAc inhibitor PKI(1-31). The mutant PKAr*, defective in binding cAMP, is shown to activate Hh target genes solely through its ability to bind and inhibit endogenous PKAc. Surprisingly, PKAcA75, a catalytically impaired mutant, also activates Hh target genes. To account for this observation, we propose that PKAc phosphorylation targeting Ci-155 for proteolysis is regulated within a complex that includes PKAc and Ci-155 and excludes PKI(1-31). This complex may permit processive phosphorylation of Ci-155 molecules, facilitating their processing to Ci-75.

scholarly journals Comprehensive analysis of micro RNAs in recurrent implantation failures patients and construction of prediction models based on circulating micro RNAs

2021 ◽  
Author(s):  
Peigen Chen ◽  
Yingchun Guo ◽  
Tingting Li ◽  
Lei Jia ◽  
Yanfang Wang ◽  
...  
Keyword(s):  
Target Genes ◽  
Prediction Models ◽  
Reproductive Technology ◽  
Control Group ◽  
Circulating Mirnas ◽  
Competing Endogenous Rna ◽  
Micro Rnas ◽  
Non Coding Rnas ◽  
Analytical Tools ◽  
The Relationship

Abstract BackgroundRecurrent implantation failure (RIF) is an obstacle in the process of assisted reproductive technology (ART). At present, there was limited research on its pathogenesis, diagnosis and treatment methods.ResultsIn this study, a series of analytical tools were used to analyze differences in miRNAs, mRNAs and lncRNAs in the endometrium of patients in the RIF group and the control group. At the same time, multiple databases are used to predict the target genes of non-coding RNAs. Then the competing endogenous RNA (ceRNA) network was built to describe the relationship between gene regulation in the endometrium of the RIF.ConcludesBased on the results of the logistic regression of co-expression miRNAs between serum and endometrial samples, we built a predictive model based on circulating miRNAs.

scholarly journals A Systematic Review and Bioinformatics Study on Genes and micro-RNAs Involving the Transformation of Endometriosis into Ovarian Cancer

MicroRNA ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 101-111
Author(s):  
Mehrdad Sheikhvatan ◽  
Shahla Chaichian ◽  
Bahram Moazzami
Keyword(s):  
Ovarian Cancer ◽  
Target Gene ◽  
Target Genes ◽  
Interaction Network ◽  
Relevant Information ◽  
Pten Gene ◽  
Mature Sequence ◽  
Micro Rnas ◽  
Bioinformatics Study ◽  
Uncontrolled Cell Proliferation

Background: Along with the description of tumorigenesis processes in endometriosisrelated ovarian cancer, identifying dysregulated miRNAs, the target genes of these miRNAs, and the processes abnormally affected by dysregulated miRNAs is essential, which was our goal. Methods: Two reviewers individually evaluated the articles which collected relevant information including genes and miRNAs involved in the transformation of endometriosis into ovarian cancer. To assess the mature sequence of miRNAs and also their chromosomal positions, miRPathDB software was employed. To determine the main target gene predicted for each considered miRNAs, the TargetScanS Web server was applied. The interaction of each gene with other genes associated with endometrial- related ovarian cancer was determined by GeneMANIA software. Finally, to design integrated model of miRNAs-targeted genes interaction network, the Cytoscape software was used. Results: The final number of studies available for analysis was 6 manuscripts including 22 miRNAs described as involved in the transformation of endometriosis into different subtypes of ovarian cancers (14 miRNAs up-regulated and 8 miRNAs down-regulated). Three miRNAs of miR-141 (upregulated), miR-205 (down-regulated), and miR-125b (down-regulated) were revealed as the originator for genetic interactions leading to carcinogenesis. We could show some common loops and pathways including uncontrolled cell proliferation and abnormal apoptosis (mediated by PTEN gene induced by miR-21 and miR-214), and disaggregation and epithelialization (mediated by ZEB1 and ZEB2 genes induced by miR-200). Conclusions: According to our analysis, up-regulation of miR-141 and down-regulation of miR-205 and miR-125b have a central role in transforming endometriosis to ovarian cancer.

scholarly journals Bioinformatics functional analysis of let-7a, miR-34a, and miR-199a/b reveals novel insights into immune system pathways and cancer hallmarks for hepatocellular carcinoma

Tumor Biology ◽  
2018 ◽  
Vol 40 (5) ◽  
pp. 101042831877367 ◽  
Author(s):  
Bangly Soliman ◽  
Ahmed Salem ◽  
Mohamed Ghazy ◽  
Nourhan Abu-Shahba ◽  
Mahmoud El Hefnawi
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune System ◽  
Signaling Pathway ◽  
Functional Annotation ◽  
Target Genes ◽  
Target Prediction ◽  
Functional Enrichment ◽  
Messenger Rnas ◽  
Micro Rnas ◽  
The Individual

Let-7a, miR-34a, and miR-199 a/b have gained a great attention as master regulators for cellular processes. In particular, these three micro-RNAs act as potential onco-suppressors for hepatocellular carcinoma. Bioinformatics can reveal the functionality of these micro-RNAs through target prediction and functional annotation analysis. In the current study, in silico analysis using innovative servers (miRror Suite, DAVID, miRGator V3.0, GeneTrail) has demonstrated the combinatorial and the individual target genes of these micro-RNAs and further explored their roles in hepatocellular carcinoma progression. There were 87 common target messenger RNAs (p ≤ 0.05) that were predicted to be regulated by the three micro-RNAs using miRror 2.0 target prediction tool. In addition, the functional enrichment analysis of these targets that was performed by DAVID functional annotation and REACTOME tools revealed two major immune-related pathways, eight hepatocellular carcinoma hallmarks–linked pathways, and two pathways that mediate interconnected processes between immune system and hepatocellular carcinoma hallmarks. Moreover, protein–protein interaction network for the predicted common targets was obtained by using STRING database. The individual analysis of target genes and pathways for the three micro-RNAs of interest using miRGator V3.0 and GeneTrail servers revealed some novel predicted target oncogenes such as SOX4, which we validated experimentally, in addition to some regulated pathways of immune system and hepatocarcinogenesis such as insulin signaling pathway and adipocytokine signaling pathway. In general, our results demonstrate that let-7a, miR-34a, and miR-199 a/b have novel interactions in different immune system pathways and major hepatocellular carcinoma hallmarks. Thus, our findings shed more light on the roles of these miRNAs as cancer silencers.

scholarly journals EP300 and SIRT1/6 Co-Regulate Lapatinib Sensitivity Via Modulating FOXO3-Acetylation and Activity in Breast Cancer

Cancers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1067 ◽  
Author(s):  
Zimam Mahmud ◽  
Ana R. Gomes ◽  
Hee Jin Lee ◽  
Sathid Aimjongjun ◽  
Yannasittha Jiramongkol ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Target Gene ◽  
Target Genes ◽  
Ectopic Expression ◽  
Sirtuin 1 ◽  
Fine Tuning ◽  
Gene Promoters ◽  
Breast Cancers ◽  
Her2 Positive ◽  
Cancer Subtypes

Forkhead Box O3 (FOXO3) is a tumor suppressor whose activity is fine-tuned by post-translational modifications (PTMs). In this study, using the BT474 breast cancer cells and a recently established lapatinib resistant (BT474-LapR) cell line, we observed that higher FOXO3 and acetylated (Ac)-FOXO3 levels correlate with lapatinib sensitivity. Subsequent ectopic expression of EP300 led to an increase in acetylated-FOXO3 in sensitive but not in resistant cells. Drug sensitivity assays revealed that sensitive BT474 cells show increased lapatinib cytotoxicity upon over-expression of wild-type but not acetylation-deficient EP300. Moreover, FOXO3 recruitment to target gene promoters is associated with target gene expression and drug response in sensitive cells and the inability of FOXO3 to bind its target genes correlates with lapatinib-resistance in BT474-LapR cells. In addition, using SIRT1/6 specific siRNAs and chemical inhibitor, we also found that sirtuin 1 and -6 (SIRT1 and -6) play a part in fine-tuning FOXO3 acetylation and lapatinib sensitivity. Consistent with this, immunohistochemistry results from different breast cancer subtypes showed that high SIRT6/1 levels are associated with constitutive high FOXO3 expression which is related to FOXO3 deregulation/inactivation and poor prognosis in breast cancer patient samples. Collectively, our results suggest the involvement of FOXO3 acetylation in regulating lapatinib sensitivity of HER2-positive breast cancers.

scholarly journals Pygo2 Associates with MLL2 Histone Methyltransferase and GCN5 Histone Acetyltransferase Complexes To Augment Wnt Target Gene Expression and Breast Cancer Stem-Like Cell Expansion

2010 ◽  
Vol 30 (24) ◽  
pp. 5621-5635 ◽  
Author(s):  
Jiakun Chen ◽  
Qicong Luo ◽  
Yuanyang Yuan ◽  
Xiaoli Huang ◽  
Wangyu Cai ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Transcriptional Activation ◽  
Cell Expansion ◽  
Breast Cancer Cells ◽  
Target Gene ◽  
Target Genes ◽  
Histone Acetyltransferase ◽  
Gene Activation ◽  
Histone Methyltransferase ◽  
T Cell Factor

ABSTRACT Resent studies have identified Pygopus as a core component of the β-catenin/T-cell factor (TCF)/lymphoid-enhancing factor 1 (LEF) transcriptional activation complex required for the expression of canonical Wg/Wnt target genes in Drosophila. However, the biochemical involvement of mammalian Pygopus proteins in β-catenin/TCF/LEF gene activation remains controversial. In this study, we perform a series of molecular/biochemical experiments to demonstrate that Pygo2 associates with histone-modifying enzymatic complexes, specifically the MLL2 histone methyltransferase (HMT) and STAGA histone acetyltransferase (HAT) complexes, to facilitate their interaction with β-catenin and to augment Wnt1-induced, TCF/LEF-dependent transcriptional activation in breast cancer cells. We identify a critical domain in Pygo2 encompassing the first 47 amino acids that mediates its HMT/HAT interaction. We further demonstrate the importance of this domain in Pygo2's ability to transcriptionally activate both artificial and endogenous Wnt target genes and to expand breast cancer stem-like cells in culture. This work now links mechanistically Pygo2's role in histone modification to its enhancement of the Wnt-dependent transcriptional program and cancer stem-like cell expansion.

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