scholarly journals Transcriptomic Analysis of L. japonicus Symbiosis Reveals New Candidate Genes for Local and Systemic Regulation of Nodule Function

Agronomy ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 819
Author(s):  
Carmen M. Pérez-Delgado ◽  
Margarita García-Calderón ◽  
María Dolores Monje-Rueda ◽  
Antonio J. Márquez ◽  
Marco Betti
Keyword(s):  
Transcription Factors ◽  
Unknown Function ◽  
Expression Profiles ◽  
Interaction Network ◽  
Differentially Expressed ◽  
Peptide Transporter ◽  
Specific Expression ◽  
Systemic Signaling ◽  
New Genes ◽  
Transporter Family

Several aspects of the legume–rhizobia symbiosis are far from being completely understood, such as the transport of compounds through the symbiosome membrane and the molecular actors (receptors, transcription factors and hormones) involved in the systemic regulation of nodulation. In this work, the transcriptomes of L. japonicus plants growing under symbiotic or non-symbiotic conditions were studied in roots and shoots, in order to look for new genes involved in nodule function and regulation both at the local and systemic levels. Several of the genes differentially expressed in roots were well-known nodulins; however, other genes with unknown function were also discovered that showed univocal nodule-specific expression profiles. Transporters of the Nitrate Transporter1/Peptide Transporter Family family, putative oligopeptide transporters, as well as other uncharacterized transporters were upregulated in nodulated roots. Five transcription factors, as well as receptors/kinases and an f-box domain containing protein, all of unknown function, were also more upregulated in nodulated roots. In the shoots of nodulated plants, genes involved in jasmonic acid and indole-3-acetic acid metabolism were differentially expressed. Moreover, three genes encoding for different glutaredoxins, proteins that were recently involved in the systemic signaling of the Arabidopsis nitrogen status, were highly downregulated in the leaves of nodulated plants. Protein–protein interaction network analysis identified nitrate reductase as a central hub in nitrogen metabolism, and a putative protein of the NADH-ubiquinone complex was highly connected to several SWEET transporters. Clustering analysis of the differentially expressed genes also suggested a possible role for a previously uncharacterized ethylene-responsive transcription factor and for LBD38 homologs in L. japonicus nodule function. The new genes identified in this study represent a promising target for the understating and manipulation of symbiotic nitrogen fixation, with the aim of improving crop legumes’ productivity.

scholarly journals Identification of hydatidosis-related modules and key regulatory genes

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9280
Author(s):  
Jijun Song ◽  
Mingxin Song
Keyword(s):  
Transcription Factors ◽  
Signaling Pathway ◽  
Target Genes ◽  
Expression Profiles ◽  
Differential Expression Analysis ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Bmp Signaling ◽  
Differentially Expressed ◽  
Regulatory Effects

Background Echinococcosis caused by larval of Echinococcus is prevalent all over the world. Although clinical experience showed that the presence of tapeworms could not be found in liver lesions, the repeated infection and aggravation of lesions still occur in the host. Here, this study constructed a multifactor-driven disease-related dysfunction network to explore the potential molecular pathogenesis mechanism in different hosts after E.multilocularis infection. Method First, iTRAQ sequencing was performed on human liver infected with E.multilocularis. Second, obtained microRNAs(miRNAs) expression profiles of humans and canine infected with Echinococcus from the GEO database. In addition, we also performed differential expression analysis, protein interaction network analysis, enrichment analysis, and crosstalk analysis to obtain genes and modules related to E.multilocularis infection. Pivot analysis is used to calculate the potential regulatory effects of multiple factors on the module and identify related non-coding RNAs(ncRNAs) and transcription factors(TFs). Finally, we screened the target genes of miRNAs of Echinococcus to further explore its infection mechanism. Results A total of 267 differentially expressed proteins from humans and 3,635 differentially expressed genes from canine were obtained. They participated in 16 human-related dysfunction modules and five canine-related dysfunction modules, respectively. Both human and canine dysfunction modules are significantly involved in BMP signaling pathway and TGF-beta signaling pathway. In addition, pivot analysis found that 1,129 ncRNAs and 110 TFs significantly regulated human dysfunction modules, 158 ncRNAs and nine TFs significantly regulated canine dysfunction modules. Surprisingly, the Echinococcus miR-184 plays a role in the pathogenicity regulation by targeting nine TFs and one ncRNA in humans. Similarly, miR-184 can also cause physiological dysfunction by regulating two transcription factors in canine. Conclusion The results show that the miRNA-184 of Echinococcus can regulate the pathogenic process through various biological functions and pathways. The results laid a solid theoretical foundation for biologists to further explore the pathogenic mechanism of Echinococcosis.

Genome-Wide Identification of differently expressed lncRNAs, mRNAs, and circRNAs in patients with osteoarthritis

2020 ◽  
Vol 15 ◽  
Author(s):  
Yeqing Sun ◽  
Lei Chen ◽  
Yingqi Zhang ◽  
Jincheng Zhang ◽  
Shashi Ranjan Tiwari
Keyword(s):  
Regulatory Networks ◽  
Expression Profiles ◽  
Interleukin 1 ◽  
Interaction Network ◽  
Circular Rna ◽  
Negative Regulation ◽  
Differentially Expressed ◽  
Positive Regulation ◽  
Proteinprotein Interaction ◽  
Differently Expressed Genes

Background: Osteoarthritis (OA), one of the most important causes leading to joint disability, was considered as an untreatable disease. A series of genes were reported to regulate the pathogenesis of OA, including microRNAs, Long non-coding RNAs and Circular RNA. So far, the expression profiles and functions of lncRNAs, mRNAs, and circRNAs in OA are not fully understood. Objective: The present study aimed to identify differently expressed genes in OA. Methods: The present study conducted RNA-seq to identify differently expressed genes in OA. Ontology (GO) analysis was used to analysis the Molecular Function and Biological Process. KEGG pathway analysis was used to perform the differentially expressed lncRNAs in biological pathways. Results: Hierarchical clustering revealed a total of 943 mRNAs, 518 lncRNAs, and 300 circRNAs were dysregulated in OA compared to normal samples. Furthermore, we constructed differentially expressed mRNAs mediated proteinprotein interaction network, differentially expressed lncRNAs mediated trans regulatory networks, and competitive endogenous RNA (ceRNA) to reveal the interaction among these genes in OA. Bioinformatics analysis revealed these dysregulated genes were involved in regulating multiple biological processes, such as wound healing, negative regulation of ossification, sister chromatid cohesion, positive regulation of interleukin-1 alpha production, sodium ion transmembrane transport, positive regulation of cell migration, and negative regulation of inflammatory response. To the best of our knowledge, this study for the first time revealed the expression pattern of mRNAs, lncRNAs and circRNAs in OA. Conclusion: This study provided novel information to validate these differentially expressed RNAs may be as possible biomarkers and targets in OA.

Irinotecan Resistance – In Search of New Markers in CRC.

2021 ◽  
Author(s):  
Jakub Kryczka ◽  
Joanna Boncela
Keyword(s):  
Drug Resistance ◽  
Cell Lines ◽  
Expression Profiles ◽  
Resistance Mechanism ◽  
Interaction Network ◽  
In Vitro Study ◽  
Cancer Drug ◽  
New Genes

Abstract Colorectal cancer (CRC) is one of the most prominent causes of cancer death worldwide. Chemotherapeutic regimens consisting of different drugs combinations such as 5-fluorouracil, and oxaliplatin (FOLFOX) or irinotecan (FOLFIRI) have been proven successful in the treatment of CRC. However, chemotherapy often leads to the acquisition of cancer drug resistance followed by metastasis and in the aftermath therapeutic failure. The molecular mechanism responsible for drug resistance is still unclear. The systemic search for new biomarkers of this phenomenon may identify new genes and pathways. To understand the drug resistance mechanism in CRC, the in vitro study based on the molecular analysis of drug-sensitive cells lines vs drug-resistant cells lines has been used. In our study to bridge the gap between in vitro and in vivo study, we compared the expression profiles of cell lines and patient samples from the publicly available database to select the new candidate genes for irinotecan resistance. Using The Gene Expression Omnibus (GEO) database of CRC cell lines (HT29, HTC116, LoVo, and their respective irinotecan-resistant variants) and patient samples (GSE42387, GSE62080, and GSE18105) we compared the changes in the mRNA expression profile of the main genes involved in irinotecan body’s processing, such as transport out of the cells and metabolism. Furthermore, using a protein-protein interaction network of differently expressed genes between FOLFIRI resistant and sensitive CRC patients, we have selected top networking proteins (upregulated: NDUFA2, SDHD, LSM5, DCAF4, and COX10, downregulated: RBM8A, TIMP1, QKI, TGOLN2, and PTGS2). Our analysis provided several potential irinotecan resistance markers, previously not described as such.

scholarly journals Genome-wide and expression analysis of B-box gene family in pepper

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Jing Ma ◽  
Jia-xi Dai ◽  
Xiao-wei Liu ◽  
Duo Lin
Keyword(s):  
Transcription Factors ◽  
Abiotic Stress ◽  
Developmental Stages ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Transient Expression Assay ◽  
Specific Expression ◽  
Tissue Specific ◽  
Duplication Events ◽  
Onion Inner Epidermis

Abstract Background BBX transcription factors are a kind of zinc finger transcription factors with one or two B-box domains, which partilant in plant growth, development and response to abiotic or biotic stress. The BBX family has been identified in Arabidopsis, rice, tomato and some other model plant genomes. Results Here, 24 CaBBX genes were identified in pepper (Capsicum annuum L.), and the phylogenic analysis, structures, chromosomal location, gene expression patterns and subcellular localizations were also carried out to understand the evolution and function of CaBBX genes. All these CaBBXs were divided into five classes, and 20 of them distributed in 11 of 12 pepper chromosomes unevenly. Most duplication events occurred in subgroup I. Quantitative RT-PCR indicated that several CaBBX genes were induced by abiotic stress and hormones, some had tissue-specific expression profiles or differentially expressed at developmental stages. Most of CaBBX members were predicated to be nucleus-localized in consistent with the transient expression assay by onion inner epidermis of the three tested CaBBX members (CaBBX5, 6 and 20). Conclusion Several CaBBX genes were induced by abiotic stress and exogenous phytohormones, some expressed tissue-specific and variously at different developmental stage. The detected CaBBXs act as nucleus-localized transcription factors. Our data might be a foundation in the identification of CaBBX genes, and a further understanding of their biological function in future studies.

scholarly journals Circular RNA Expression Profiles and Features in NAFLD Mice: A Study Using RNA-Seq Data

2020 ◽  
Author(s):  
Xinlu Yuan ◽  
Jianjun Diao ◽  
Anqing Du ◽  
Song Wen ◽  
Ligang Zhou ◽  
...  
Keyword(s):  
Expression Profile ◽  
Noncoding Rna ◽  
Expression Profiles ◽  
Circular Rna ◽  
Differentially Expressed ◽  
Rna Seq ◽  
Mice Model ◽  
Specific Expression ◽  
Nonalcoholic Fatty Liver ◽  
Sequencing Method

Abstract Background: Nonalcoholic fatty liver disease (NAFLD) is primarily characterized by the hepatic cholesterol accumulation. Circular RNA (circRNA), one of noncoding RNA, involves in many liver diseases progression. However, no recent studies on circRNA expression profiles in NAFLD have been reported previously.Methods: A NAFLD mouse model was constructed by providing high-fat diet (HFD) for 32 weeks. The circRNAs expression profile in normal mice and NAFLD mice were determined using high-output RNA sequencing method and bioinformatics methods, while the differentially expressed circRNAs were confirmed using Sanger sequencing and qRT-PCR. The circRNA-miRNA network was also predicted. The biological functions of circRNAs were annotated by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG).Results: The results demonstrated the successful construction of NAFLD mice model by immunohistology and serology assay. In total, 93 dysregulated circRNAs were observed, including 57 upregulated circRNAs and 36 downregulated circRNAs, in the NAFLD group. The circRNA-miRNA network revealed the complex interaction between circRNAs and its potential miRNA targets in NAFLD. The characteristic of tissue-specific expression in circRNA was demonstrated. The differentially expressed circRNAs with important biological function were also annotated using GO and KEGG. Both DDAH1 and VAV3 genes were found to be associated with the NAFLD development.Conclusions: Taken together, this study demonstrated the circRNAs expression profile and features in NAFLD, which may provide potential biological markers for the pathogenesis of NAFLD.

scholarly journals Reduced Expression of Slc Genes in the VTA and NAcc of Male Mice with Positive Fighting Experience

2020 ◽  
Author(s):  
Dmitry A. Smagin ◽  
Vladimir N. Babenko ◽  
Irina L. Kovalenko ◽  
Anna G. Galyamina ◽  
Olga E. Redina ◽  
...  
Keyword(s):  
Expression Profiles ◽  
Differentially Expressed ◽  
Male Mice ◽  
Agonistic Interactions ◽  
Specific Expression ◽  
Chronic Stimulation ◽  
Altered Expression ◽  
Slc Transporters ◽  
Genes Encoding ◽  
Complete Disruption

ABSTRACTThere are many psychiatric medications targeting the activity of SLC transporters. Therefore, further research is needed to elucidate the expression profiles of the Slc* genes, which may serve as markers of altered brain metabolic processes and neurotransmitter activities in psychoneurological disorders. We studied differentially expressed Slc genes using the transcriptomic profiles in the ventral tegmental area (VTA), nucleus accumbens (NAcc), and prefrontal cortex (PFC) of male mice with psychosis-like behavior induced by repeated aggression experience in daily agonistic interactions which are accompanied by wins. Most of differentially expressed Slc genes in the VTA and NAcc (12 of 17 and 25 of 26, respectively) were downregulated, which was not the case in the PFC (6 and 5, up- and down, respectively). Also, the majority of these genes were shown to have brain region-specific expression profiles. In the VTA and NAcc altered expression was observed for the genes encoding the transporters of neurotransmitters as well as inorganic and organic ions, amino acids, metals, glucose, etc. This means alteration in transport functions for many substrates, which results in complete disruption of all cellular and neurotransmitter processes. The neurotransmitter systems, especially, the dopaminergic one, in male mice with positive fighting experience in daily agonistic interactions undergo changes leading to profound genomic modifications which include downregulated expression of the majority of the Slc* genes at least in the VTA and NAcc, which is attributable to chronic stimulation of the reward systems.

scholarly journals Genome-wide identification and comparison of differentially expressed profiles of miRNAs and lncRNAs with associated ceRNA networks in the gonads of Chinese soft-shelled turtle, Pelodiscus sinensis

2020 ◽  
Author(s):  
Xiao Ma ◽  
Shuangshuang Cen ◽  
Luming Wang ◽  
Chao Zhang ◽  
Limin Wu ◽  
...  
Keyword(s):  
Messenger Rna ◽  
Target Genes ◽  
Expression Profiles ◽  
Differentially Expressed ◽  
Integrated Analysis ◽  
Pelodiscus Sinensis ◽  
Specific Expression ◽  
Protein Coding ◽  
Reproductive Regulation ◽  
Protein Coding Genes

Abstract Background: The gonad is the major factor affecting animal reproduction. The regulatory mechanism of the expression of protein-coding genes involved in reproduction still remains to be elucidated. Increasing evidence has shown that ncRNAs play key regulatory roles in gene expression in many life processes. The roles of microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) in reproduction have been investigated in some species. However, the regulatory patterns of miRNA and lncRNA in the sex biased expression of protein coding genes remains to be elucidated. In this study, we performed an integrated analysis of miRNA, messenger RNA (mRNA), and lncRNA expression profiles to explore their regulatory patterns in the female ovary and male testis of Chinese soft-shelled turtle, Pelodiscus sinensis.Results: We identified 10 446 mature miRNAs, 20 414 mRNAs and 28 500 lncRNAs in the ovaries and testes, and 633 miRNAs, 11 319 mRNAs, and 10 495 lncRNAs showed differential expression. A total of 2 814 target genes were identified for miRNAs. The predicted target genes of these differentially expressed (DE) miRNAs and lncRNAs included abundant genes related to reproductive regulation. Furthermore, we found that 189 DEmiRNAs and 5 408 DElncRNAs showed sex-specific expression. Of these, 3 DEmiRNAs and 917 DElncRNAs were testis-specific, and 186 DEmiRNAs and 4 491 DElncRNAs were ovary-specific. We further constructed complete endogenous lncRNA-miRNA-mRNA networks using bioinformatics, including 103 DEmiRNAs, 636 DEmRNAs, and 1 622 DElncRNAs. The target genes for the differentially expressed miRNAs and lncRNAs included abundant genes involved in gonadal development, including Wt1, Creb3l2, Gata4, Wnt2, Nr5a1, Hsd17, Igf2r, H2afz, Lin52, Trim71, Zar1, and Jazf1.Conclusions: In animals, miRNA and lncRNA as master regulators regulate reproductive processes by controlling the expression of mRNAs. Considering their importance, the identified miRNAs, lncRNAs, and their targets in P. sinensis might be useful for studying the molecular processes involved in sexual reproduction and genome editing to produce higher quality aquaculture animals. A thorough understanding of ncRNA-based cellular regulatory networks will aid in the improvement of P. sinensis reproductive traits for aquaculture.

scholarly journals Identification of lncRNA–mRNA Regulatory Network Associated With Isolated Systolic Hypertension and Atherosclerotic Cerebral Infarction

2021 ◽  
Author(s):  
jie Yang ◽  
Yan-Nan Tao ◽  
Fang-Xiao Hu ◽  
Yong-Zhi Chen ◽  
Xue-Song Yang ◽  
...  
Keyword(s):  
Cerebral Infarction ◽  
Regulatory Network ◽  
Systolic Hypertension ◽  
Expression Profiles ◽  
Pearson Correlation ◽  
Interaction Network ◽  
Differentially Expressed ◽  
Isolated Systolic Hypertension ◽  
Hub Genes ◽  
Qrt Pcr

Abstract Background: Increasing evidences uncover that lncRNAs play an important role in Isolated systolic hypertension (ISH). However, a systematic lncRNA-mRNA regulatory network is still absent in isolated systolic hypertension and atherosclerotic cerebral infarction patients (ISH & ACI).Aim:This research aims to establish a lncRNA-mRNA co-expression network in patients with ISH & ACI, to probe into the potential functions of lncRNA in those patients.Design and Setting:Expression profiles of lncRNA and mRNAs are collected and compared respectively from 8 patients with ISH and 8 patients with ISH & ACI by RNA-seq data.Methods: Differentially expressed lncRNAs and mRNAs were screened out via high-throughput sequencing in the plasma of ISH/ACI patients and control ISH patients. Then, a lncRNA-mRNA interaction network was built using the Pearson correlation coefficient by Cytoscape software. The expression levels of the hub genes and lncRNAs were verified by qRT-PCR in another 10 ISH/ACI patients and 10 control patients. Results: 2768 differentially expressed lncRNAs and 747 differentially expressed mRNAs were identified. 2 hub genes (CD226 and PARVB) and 11 lncRNAs were identified in the lncRNA-mRNA interaction network. qRT-PCR and cell assay results verified that lncRNAs ENST00000590604 and CD226 are highly expressed in patients of ISH & ACI. CD226 was associated with vascular endothelial cells growth and stability through platelet activation and focal adhesion pathway.Conclusion: We established a novel mRNA-lncRNA interaction network. lncRNAs ENST00000590604 and CD226 might be the potential biomarkers of ISH & ACI.

The MDS-Associated Gene DLK Modulates Gene Expression in Human Myeloid Cells by Altering the Activity of Multiple Transcription Factors.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3428-3428
Author(s):  
Liang Li ◽  
Rushabh Modi ◽  
Xiwei Wu ◽  
Stephen J. Forman ◽  
Ravi Bhatia
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Cell Differentiation ◽  
Linear Model ◽  
Expression Profiles ◽  
Myeloid Cells ◽  
Gene Expression Profiles ◽  
Differentially Expressed ◽  
Differentiation And Proliferation ◽  
And Control

Abstract Delta-Like 1 (DLK) is an EGF-like transmembrane protein, which is overexpressed in myelodysplastic syndrome (MDS) CD34+ cells. We have previously shown that ectopic DLK expression inhibits HL-60 cell differentiation and proliferation through intracellular domain interactions. To further investigate mechanisms underlying DLK effects on myeloid cell differentiation and proliferation, we compared gene expression profiles of DLK expressing and control HL-60 cells, with or without differentiating induction with ATRA, using Affymetrix HG-U133A arrays. Gene expression data was analyzed using affy and limma (linear model of microarray analysis) packages in the open-source BioConductor project (v 1.6). Raw data were processed using robust multi-chip average (RMA) algorithm, a linear model fit to each gene, and the following comparisons were made: (a) effects of DLK expression in unstimulated cells, (b) effects of DLK expression in ATRA exposed cells, (c) effects of ATRA induction on R1 cells, (d) effects of ATRA induction on DLK+ cells, and (e) differences in the response of DLK+ vs. control cells to ATRA. Adjusted P values and log odds of differential expression (B statistic, 50% probability when B=0) were calculated. B values > 0 were considered statistically significant. 523 genes were differentially expressed between unstimulated control and DLK+ cells, 343 genes were differentially expressed between control and DLK+ cells after ATRA stimulation, and 204 genes were common to the two sets. 802 genes were differentially expressed after ATRA stimulation in control cells, 742 genes in DLK+ cells, with 550 genes common to the two sets. 13 genes were differentially expressed when ATRA responses of control and DLK+ cells were compared. Gene ontology (GO) analyses indicated that "Biological processes" significantly affected by DLK overexpression included signal transduction, cell cycle, proliferation, cell death, protein metabolism and enzyme cascades, and "Molecular functions" most affected included nucleotide/DNA binding and protein kinase activity. These observations are consistent with observed cellular effects of DLK. Using MotifRegressor software, we performed promoter analysis correlating common transcription factor-binding motifs with expression profiles of genes differentially expressed between DLK+ and control cells. We identified the transcription factors (TF) PBX, GATA-1, c-Myc: Max, HIF-1, DEC1, Hand1, Lmo2, NKX25, GKLF and AP-1 as being potentially involved in DLK-mediated changes in gene expression. The observed patterns of differential gene expression were consistent with altered activities of these TF. Electrophoresis mobility shift assays (EMSA) indicated increased PBX and reduced HIF-1 and GATA-1 activities in DLK+ cells. Interestingly, Hand1, c-Myc: Max and Dec1 are basic Helix-loop-Helix (b-HLH) factors with E box binding sites, which are known to associate and form regulatory complexes with other TF. TF such as GATA-1, GLKF and Lmo2, also identified in our analysis, are known to be associated with such complexes. In conclusion, gene expression profiles of DLK expressing human myeloid cells are consistent with observed alterations in cell proliferation and differentiation. We have identified TF that may act individually and/or in concert to induce the observed changes in gene expression in DLK+ cells. Further evaluation of their role of these TF in mediating DLK effects and in abnormal hematopoietic cell growth in MDS is warranted.

MiRNA Expression Signatures in Acute Myeloid Leukemia Are Predictors for Patient Outcome.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 152-152
Author(s):  
Thomas Illmer ◽  
David Kosel ◽  
Markus A. Schaich ◽  
Christian Thiede ◽  
Andreas Neubauer ◽  
...  
Keyword(s):  
Microarray Data ◽  
Mirna Expression ◽  
Expression Profiles ◽  
Stem Cell Differentiation ◽  
Chromosome 7 ◽  
Differentially Expressed ◽  
Specific Expression ◽  
Monosomy 7 ◽  
Median Expression

Abstract Only recently, a class of gene regulatory molecules (miRNA’s) has been described that have the potential for posttranscriptional and translational gene regulation. MiRNA’s can influence critical cellular properties like proliferation and differentiation. Since these properties vary substantially in genetically defined AML subsets we have chosen to analyze AML patients with inv(16) (n=12); standard risk cytogenetic classification (mainly comprising the normal karyotype) (SR) (n=21) and with monosomy 7 or deletion7q (n=17) using DNA oligonucleotide arrays which are employing the mirVANA miRNA probe set. Principal Component Analysis (PCA) of AML samples from patients with inv(16) showed only minor differences to normal bone marrow (BM). In contrast AML patients with SR could be clearly divided in two subgroups - one subgroup that showed miRNA expression pattern close to BM and a distinctly different subgroup. Comparison of SR patient samples with BM using ANOVA tests revealed 9 differentially expressed miRNA’s (mir-223; mir-15a; mir-16; mir-203; mir-103; mir-23b; mir-107, mir-17–5p and mir23a). AML patients with aberrations of chromosome 7 showed highly distinct PCA pattern as compared to BM samples. 64 miRNA’s were found to be differentially expressed in those patients as compared to BM. All miRNA’s located on chromosome7 that were included in the array were found downregulated in AML patients with aberrant chromosome 7 (e.g.mir-335). To further substantiate the microarray data we analyzed a total of 108 AML patients with inv(16), SR cytogenetics and aberrations of chromosome 7 for mir-23a, mir-223, mir-16 and mir-335 expression by qRT-PCR. Supporting the microarray data it could be shown that the median expression levels of mir-23a, mir-223 and mir-16 were lowest in patients with SR cytogenetics, whereas AML patients with chromosome 7 aberrations showed lowest median expression for mir-335 transcripts. This was in clear contrast to the expression of mir-150, a miRNA which could be previously shown to associate with immature T-cells and which had the highest expression in AML samples with chromosome 7 aberrations. Expression of mir-150 was correlated with a high CD34 percentage in the investigated AML samples (p<0.001) whereas mir-223 did not correlate with CD34 but was strongly associated with the surface expression of CD14 (p<0.001). In an in-vitro model of G-CSF induced CD34+ stem cell differentiation mir-223 and mir-16 were slightly upregulated whereas mir-150 disappeared during the process of differentiation. Finally, the investigated miRNA were entered in a model for outcome prediction in AML samples with SR cytogenetics including known risk factors. Within this model the ratio of mutant vs. wt FLT-3 was the strongest predictor of overall survival (p<0.01). Additonally, mir-23a expression proved to be an independent negative prognostic factor for AML patients with SR cytogenetics (p<0.05). In conclusion, the presented data demonstrate specific expression profiles of miRNA’s in AML patients with different cytogenetic risk profiles. As it could be shown for patients with SR cytogenetics the observed expression profiles are likely to contribute to a deregulated differentiation and may influence therapeutic outcome.

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