Profiling of Exosomal MicroRNAs Expression in Umbilical Cord Blood from Normal and Preeclampsia Patients

Abstract Background: Epidemiological and experimental studies suggest that preeclampsia has a negative impact on maternity and offspring health. Previous studies report that dysregulation in utero-environment increases risk for elderly disease such as cardiovascular disease. However, the underlying mechanisms remain elusive. Specific microRNAs (miRNAs) are packaged in exosomes may regulate processes in offspring microvascular dysfunction.Methods: A comprehensive miRNA sequence-based approach to compare exosomes carry miRNAs (Exo-miRNAs) expression levels in umbilical serum between normal and preeclampsia patients was performed to explore mechanisms for development of cardiovascular dysfunction in offspring exposed to preeclampsia. by ExoQuick precipitations were used to isolate serum exosomes. Serum exosomes were then viewed under electron microscopy, and their characteristics determined by western blotting and nanoparticle-tracking analysis. Illumina platform was used to perform sequencing. Bioinformatics analysis was used to explore differentially expressed Exo-miRNAs in umbilical serum.Results: Based on sequence similarity, 1733 known miRNAs were retrieved. Furthermore, 157 mature miRNAs in serum exosomes were significantly differential expressed between PE and those control groups (P＜0.05, log2|FC|>1). Out, of the 157 miRNAs, 96 were upregulated miRNAs whereas 61 miRNAs were downregulated. The 157 differentially expressed miRNAs targeted 51424 differentially expressed genes. Functional analysis through KEGG pathway and Gene Ontology results uncovered that target genes of miRNAs with differential expression were significantly linked to several pathways and biological processes.Conclusion: The findings of this study showed differential expression of umbilical serum Exo-miRNAs in normal compared with PE patients, implying that these Exo-miRNAs play an important function in offspring microvascular dysfunction of preeclampsia.

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Epigenetic Mechanism and Survival Prognosis Analysis of Serum Exosomes from Ovarian Cancer Patients based on Sequencing Technology and Bioinformatics

10.21203/rs.3.rs-981954/v1 ◽

2021 ◽

Author(s):

Li Xia ◽

Huang He

Keyword(s):

Ovarian Cancer ◽

Cancer Patients ◽

Target Genes ◽

Epigenetic Modification ◽

Gene Prediction ◽

Enrichment Analysis ◽

Differentially Expressed ◽

Survival Prognosis ◽

Signaling Axis ◽

Serum Exosomes

Abstract Backguound: To screen the signaling axis of epigenetic modification in serum exosomes of ovarian cancer patients based on sequencing technology and raw signal analysis, in depth study of the potential mechanism of action of ovarian cancer, prediction of potential therapeutic targets and survival prognosis analysis of potential targets.Methods: Serum exosomes from three ovarian cancer patients were selected as the experimental group, and serum exosomes from three uterine fibroid patients as the control group, and whole transcriptome of serum exosomes was performed to obtain differentially expressed lncRNA and mRNA in ovarian cancer,The miRcode database and miRNA target gene prediction website were used to predict the target genes, Cytoscape software was used to draw a ceRNA network model of epigenetic modification of ovarian cancer serum exosomes, and the R language was used for GO and KEGG enrichment analysis of the target genes. Finally, the TCGA website was used to download clinical and expression data related to ovarian cancer, and the common potential target genes obtained in the previous period were analyzed for survival。Results: A total of 117 differentially expressed lncRNAs as well as 513 differentially expressed mRNAs (P < 0.05, |log2 FC|≥ 1.0) were obtained by combining sequencing data and raw signal analysis, and 841 predicted target genes were reciprocally mapped by combining mircode database and miRNA target gene prediction website, resulting in 11 potential target genes related to ovarian cancer (FGFR3, BMPR1B, TRIM29, FBN2, PAPPA, CCDC58, IGSF3, FBXO10, GPAM, HOXA10, LHFPL4), and survival prognosis analysis of the above 11 target genes revealed that the survival curve was statistically significant (P < 0.05) for HOXA10 only genes, but not for the other genes, and through enrichment analysis, we found that the above target genes were mainly involved in biological processes such as regulation of transmembrane receptor protein kinase activity, structural molecule activity with elasticity, transforming growth factor - activated receptor activity, and GABA receptor binding, and were mainly enriched in signaling pathways regulating stem cell pluripotency, bladder cancer, glycerolipid metabolism, central carbon metabolism of cancer, tyrosine stimulation to EGFR in signaling pathways such as resistance to enzyme inhibitors.Conclusions: The serum exosomal DIO3OS-hsa-miR-27a-3p-HOXA10 epigenetic modification signaling axis affects ovarian cancer development and disease survival prognosis by targeting transcriptional dysregulation pathways in cancer.

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MicroRNA sequence analysis identifies microRNAs associated with peri-implantitis in dogs

Bioscience Reports ◽

10.1042/bsr20170768 ◽

2017 ◽

Vol 37 (5) ◽

Cited By ~ 10

Author(s):

Xiaolin Wu ◽

Xipeng Chen ◽

Wenxiang Mi ◽

Tingting Wu ◽

Qinhua Gu ◽

...

Keyword(s):

Sequence Analysis ◽

Target Genes ◽

Alveolar Bone ◽

Biological Effects ◽

Bone Destruction ◽

Mapk Signaling ◽

Differentially Expressed ◽

Mitogen Activated Protein Kinase ◽

Mirna Sequence ◽

Differentially Expressed Mirnas

Peri-implantitis, which is characterized by dense inflammatory infiltrates and increased osteoclast activity, can lead to alveolar bone destruction and implantation failure. miRNAs participate in the regulation of various inflammatory diseases, such as periodontitis and osteoporosis. Therefore, the present study aimed to investigate the differential expression of miRNAs in canine peri-implantitis and to explore the functions of their target genes. An miRNA sequence analysis was used to identify differentially expressed miRNAs in peri-implantitis. Under the criteria of a fold-change >1.5 and P<0.01, 8 up-regulated and 30 down-regulated miRNAs were selected for predictions of target genes and their biological functions. Based on the results of Gene Ontology (GO) and KEGG pathway analyses, these miRNAs may fine-tune the inflammatory process in peri-implantitis through an intricate mechanism. The results of quantitative real-time PCR (qRT-PCR) revealed that let-7g, miR-27a, and miR-145 may play important roles in peri-implantitis and are worth further investigation. The results of the present study provide insights into the potential biological effects of the differentially expressed miRNAs, and specific enrichment of target genes involved in the mitogen-activated protein kinase (MAPK) signaling pathway was observed. These findings highlight the intricate and specific roles of miRNAs in inflammation and osteoclastogenesis, both of which are key aspects of peri-implantitis, and thus may contribute to future investigations of the etiology, underlying mechanism, and treatment of peri-implantitis.

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Screening candidate microR-15a- IRAK2 regulatory pairs for predicting the response to Staphylococcus aureus-induced mastitis in dairy cows

Journal of Dairy Research ◽

10.1017/s0022029919000785 ◽

2019 ◽

Vol 86 (4) ◽

pp. 425-431 ◽

Cited By ~ 3

Author(s):

Zhi Chen ◽

Jingpeng Zhou ◽

Xiaolong Wang ◽

Yang Zhang ◽

Xubin Lu ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Differential Expression ◽

High Throughput Sequencing ◽

Target Genes ◽

Interleukin 1 ◽

Differentially Expressed ◽

Luciferase Reporter ◽

Expression Of Genes ◽

Chinese Holstein Cows ◽

Reporter Assays

AbstractWe established a mastitis model using exogenous infection of the mammary gland of Chinese Holstein cows with Staphylococcus aureus and extracted total RNA from S. aureus-infected and healthy mammary quarters. Differential expression of genes due to mastitis was evaluated using Affymetrix technology and results revealed a total of 1230 differentially expressed mRNAs. A subset of affected genes was verified via Q-PCR and pathway analysis. In addition, Solexa high-throughput sequencing technology was used to analyze profiles of miRNA in infected and healthy quarters. These analyses revealed a total of 52 differentially expressed miRNAs. A subset of those results was verified via Q-PCR. Bioinformatics techniques were used to predict and analyze the correlations among differentially expressed miRNA and mRNA. Results revealed a total of 329 pairs of negatively associated miRNA/mRNA, with 31 upregulated pairs of mRNA and 298 downregulated pairs of mRNA. Differential expression of miR-15a and interleukin-1 receptor-associated kinase-like 2 (IRAK2), were evaluated by western blot and luciferase reporter assays. We conclude that miR-15a and miR-15a target genes (IRAK2) constitute potential miRNA–mRNA regulatory pairs for use as biomarkers to predict a mastitis response.

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Peripheral Circulating Exosomal miRNAs Potentially Contribute to the Regulation of Molecular Signaling Networks in Aging

International Journal of Molecular Sciences ◽

10.3390/ijms21061908 ◽

2020 ◽

Vol 21 (6) ◽

pp. 1908 ◽

Cited By ~ 3

Author(s):

Hongxia Zhang ◽

Kunlin Jin

Keyword(s):

Target Genes ◽

Differentially Expressed ◽

Molecular Signaling ◽

Slow Development ◽

Exosomal Mirnas ◽

Pathways Analysis ◽

Old Rats ◽

Underlying Mechanisms ◽

Signaling Components ◽

Serum Exosomes

People are living longer than ever. Consequently, they have a greater chance for developing a functional impairment or aging-related disease, such as a neurodegenerative disease, later in life. Thus, it is important to identify and understand mechanisms underlying aging as well as the potential for rejuvenation. Therefore, we used next-generation sequencing to identify differentially expressed microRNAs (miRNAs) in serum exosomes isolated from young (three-month-old) and old (22-month-old) rats and then used bioinformatics to explore candidate genes and aging-related pathways. We identified 2844 mRNAs and 68 miRNAs that were differentially expressed with age. TargetScan revealed that 19 of these miRNAs are predicated to target the 766 mRNAs. Pathways analysis revealed signaling components targeted by these miRNAs: mTOR, AMPK, eNOS, IGF, PTEN, p53, integrins, and growth hormone. In addition, the most frequently predicted target genes regulated by these miRNAs were EIF4EBP1, insulin receptor, PDK1, PTEN, paxillin, and IGF-1 receptor. These signaling pathways and target genes may play critical roles in regulating aging and lifespan, thereby validating our analysis. Understanding the causes of aging and the underlying mechanisms may lead to interventions that could reverse certain aging processes and slow development of aging-related diseases.

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Differential expression of family with sequence similarity 13 member C in cancers of the breast.

10.31219/osf.io/8kasv ◽

2021 ◽

Author(s):

Shahan Mamoor

Keyword(s):

Breast Cancer ◽

Differential Expression ◽

Survival Data ◽

Molecular Subtype ◽

Sequence Similarity ◽

Differentially Expressed Gene ◽

Normal Breast ◽

Differentially Expressed ◽

Significant Differential Expression ◽

Primary Tumors

Breast cancer affects women at relatively high frequency (1). We mined published microarray datasets (2, 3) to determine in an unbiased fashion and at the systems level genes most differentially expressed in the primary tumors of patients with breast cancer. We report here significant differential expression of the gene encoding family with sequence similarity 13 member C, FAM13C, when comparing primary tumors of the breast to the tissue of origin, the normal breast. FAM13C mRNA was present at significantly lower quantities in tumors of the breast as compared to normal breast tissue. Analysis of human survival data revealed that expression of FAM13C in primary tumors of the breast was correlated with overall survival in patients with HER2+ cancers, demonstrating a relationship between primary tumor expression of a differentially expressed gene and patient survival outcomes influenced by molecular subtype. FAM13C may be of relevance to initiation, maintenance or progression of cancers of the female breast.

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MACE-Seq-based coding RNA and TrueQuant-based small RNA profile in breast cancer: tumor-suppressive miRNA-1275 identified as a novel marker

BMC Cancer ◽

10.1186/s12885-021-08218-4 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Sevan Omer Majed ◽

Suhad Asad Mustafa

Keyword(s):

Breast Cancer ◽

Differential Expression ◽

Small Rnas ◽

Target Genes ◽

Target Prediction ◽

Ffpe Tissue ◽

Differentially Expressed ◽

Expression Level ◽

Formalin Fixed Paraffin Embedded ◽

Cancer Tumor

Abstract Introduction Disruption of cellular processes in the breast by abnormally expressed miRNA is characterized to develop cancer. We aimed to identify the differential expression of small RNAs (sRNAs) and mRNAs in formalin-fixed paraffin-embedded (FFPE) tissue of the breast cancer (BC) and normal adjacent tissue (NAT). Another aim is to determine the differential expression of miR-1275 as a novel biomarker for BC and also identify its target genes. Methods TrueQuant method for analysis of sRNA expression and MACE-sequencing method for analysis of gene expression were used analyzing. The RT-qPCR technique was used to confirm miR-1275 down expression. Target genes of miR-1275 were computationally identified using target prediction sites and also the expression level of them was experimentally determined among the expressed genes. Results TrueQuant findings showed that 1400 sRNAs were differentially expressed in the FFPE tissue of two Kurdish cases with BC, as compared to NAT. Among the sRNAs, 29 small RNAs were shown to be significantly downregulated in BC cells. The RT-qPCR results confirmed that miR-1275 was significantly down-expressed in 20 Kurdish cases with BC compared to NAT. However, Overall survival (OS) analysis revealed that the correlation between the expression level of miR-1275 and clinical significance was highly corrected in cases with BC (OS rate: P = 0.0401). The MACE-seq results revealed that 26,843 genes were differentially expressed in the BC tissue compared to NAT, but 7041 genes were displayed in a scatter plot. Furthermore, putative target genes (DVL3, PPP2R2D, THSD4, CREB1, SYT7, and PRKACA) were computationally identified as direct targets of miR-1275 in several target predicted sites. The MACE-seq results revealed that the expression level of these targets was increased in BC tissue compared to NAT. The level of these targets was negatively associated with miR-1275 expression. Finally, the role of down-regulated miR-1275 on its targets in biological mechanisms of BC cells was identified; including cell growth, proliferation, movement, invasion, metastasis, and apoptosis. Conclusion Down-expressed miR-1275, a tumor suppressor, is a novel biomarker for early detection of BC. DVL3, PPP2R2D, THSD4, CREB1, SYT7, and PRKACA are newly identified to be targeted by miR-1275.

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Exploring microRNA target genes and identifying hub genes in bladder cancer based on bioinformatic analysis

BMC Urology ◽

10.1186/s12894-021-00857-w ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Hongjian Wu ◽

Wubing Jiang ◽

Guanghua Ji ◽

Rong Xu ◽

Gaobo Zhou ◽

...

Keyword(s):

Bladder Cancer ◽

Differential Expression ◽

Expression Analysis ◽

Target Genes ◽

Cancer Genomics ◽

Differential Expression Analysis ◽

Gene Set Enrichment Analysis ◽

Differentially Expressed ◽

Tumour Suppressor Genes ◽

Hub Genes

Abstract Background Bladder cancer (BC) is the second most frequent malignancy of the urinary system. The aim of this study was to identify key microRNAs (miRNAs) and hub genes associated with BC as well as analyse their targeted relationships. Methods According to the microRNA dataset GSE112264 and gene microarray dataset GSE52519, differentially expressed microRNAs (DEMs) and differentially expressed genes (DEGs) were obtained using the R limma software package. The FunRich software database was used to predict the miRNA-targeted genes. The overlapping common genes (OCGs) between miRNA-targeted genes and DEGs were screened to construct the PPI network. Then, gene ontology (GO) analysis was performed through the “cluster Profiler” and “org.Hs.eg.db” R packages. The differential expression analysis and hierarchical clustering of these hub genes were analysed through the GEPIA and UCSC Cancer Genomics Browser databases, respectively. KEGG pathway enrichment analyses of hub genes were performed through gene set enrichment analysis (GSEA). Results A total of 12 DEMs and 10 hub genes were identified. Differential expression analysis of the hub genes using the GEPIA database was consistent with the results for the UCSC Cancer Genomics Browser database. The results indicated that these hub genes were oncogenes, but VCL, TPM2, and TPM1 were tumour suppressor genes. The GSEA also showed that hub genes were most enriched in those pathways that were closely associated with tumour proliferation and apoptosis. Conclusions In this study, we built a miRNA-mRNA regulatory targeted network, which explores an understanding of the pathogenesis of cancer development and provides key evidence for novel targeted treatments for BC.

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Analysis of miRNAs Profiles in Serum of Patients With Steatosis and Steatohepatitis

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.736677 ◽

2021 ◽

Vol 9 ◽

Author(s):

Maria Vulf ◽

Daria Shunkina ◽

Aleksandra Komar ◽

Maria Bograya ◽

Pavel Zatolokin ◽

...

Keyword(s):

Epigenetic Regulation ◽

Target Genes ◽

Experimental Studies ◽

Enrichment Analysis ◽

Gene Set Enrichment Analysis ◽

Differentially Expressed ◽

World Population ◽

Alcoholic Fatty Liver ◽

New Findings ◽

Differentially Expressed Mirnas

Non-alcoholic fatty liver disease (NAFLD) is emerging as one of the most common chronic liver diseases worldwide, affecting 25% of the world population. In recent years, there has been increasing evidence for the involvement of microRNAs in the epigenetic regulation of genes taking part in the development of steatosis and steatohepatitis—two main stages of NAFLD pathogenesis. In the present study, miRNA profiles were studied in groups of patients with steatosis and steatohepatitis to compare the characteristics of RNA-dependent epigenetic regulation of the stages of NAFLD development. According to the results of miRNA screening, 23 miRNAs were differentially expressed serum in a group of patients with steatohepatitis and 2 in a group of patients with steatosis. MiR-195-5p and miR-16-5p are common differentially expressed miRNAs for both steatosis and steatohepatitis. We analyzed the obtained results: the search for target genes for the differentially expressed miRNAs in our study and the subsequent gene set enrichment analysis performed on KEGG and REACTOME databases revealed which metabolic pathways undergo changes in RNA-dependent epigenetic regulation in steatosis and steatohepatitis. New findings within the framework of this study are the dysregulation of neurohumoral pathways in the pathogenesis of NAFLD as an object of changes in RNA-dependent epigenetic regulation. The miRNAs differentially expressed in our study were found to target 7% of genes in the classic pathogenesis of NAFLD in the group of patients with steatosis and 50% in the group of patients with steatohepatitis. The effects of these microRNAs on genes for the pathogenesis of NAFLD were analyzed in detail. MiR-374a-5p, miR-1-3p and miR-23a-3p do not target genes directly involved in the pathogenesis of NAFLD. The differentially expressed miRNAs found in this study target genes largely responsible for mitochondrial function. The role of miR-423-5p, miR-143-5p and miR-200c-3 in regulating apoptotic processes in the liver and hepatocarcinogenesis is of interest for future experimental studies. These miR-374a, miR-143, miR-1, miR-23a, and miR-423 have potential for steatohepatitis diagnosis and are poorly studied in the context of NAFLD. Thus, this work opens up prospects for further studies of microRNAs as diagnostic and therapeutic biomarkers for NAFLD.

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Comparative Transcriptomes Analysis of Taenia pisiformis at Different Development Stages

10.1101/490276 ◽

2018 ◽

Cited By ~ 1

Author(s):

Lin Chen ◽

Yu Jing ◽

Jing Xu ◽

Wei Wang ◽

Lily Ji ◽

...

Keyword(s):

Differentially Expressed Genes ◽

Target Genes ◽

Developmental Stages ◽

Sequence Similarity ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Differentially Expressed ◽

Bioinformatic Tools ◽

Sequence Similarity Analysis ◽

Two Stages

To understand the characteristics of the transcriptional group of Taenia pisiformis at different developmental stages, and to lay the foundation for the screening of vaccine antigens and drug target genes, the transcriptomes of adult and larva of T. pisiformis were assembled and analyzed using bioinformatic tools. A total of 36,951 unigenes with a mean length of 950bp were formed, among which 12,665, 8,188, 7,577, and 6,293 unigenes have been annotated respectively by sequence similarity analysis with four databases (NR, Swiss-Prot, KOG, and KEGG). It should be noted there are 5,662 unigenes that share good similarity with the four databases and get a relatively perfect functional annotation. Besides, a total of 10,247 differentially expressed genes were screened. To be specific, 6,910 unigenes were up-regulated in the larva stage while 3,337 were down-regulated in the adult stage. To sum up, this study sequenced and analyzed the transcriptomes of the larval and adult stages of T. pisiformis. The results of differentially expressed genes in these two stages could provide basis for functional genomics, immunology and gene expression profiles of T. pisiformis.

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Differential expression of micro-RNA in tumor and non-tumor tissues of patients with colorectal cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e13516 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e13516-e13516

Author(s):

Inna A. Novikova ◽

Natalya N. Timoshkina ◽

Oleg Ivanovich Kit ◽

Sergey I. Poluektov ◽

Andrey V. Dashkov ◽

...

Keyword(s):

Gene Expression ◽

Colorectal Cancer ◽

Differential Expression ◽

Tumor Markers ◽

Target Genes ◽

Tumor Tissue ◽

Micro Rna ◽

Differentially Expressed ◽

Tumor Tissues ◽

Micro Rnas

e13516 Background: The colorectal cancer (CRC) incidence is steadily increasing. Moreover, the problem of its early diagnosis remains unresolved due to the low specificity of known tumor markers, and the problem of creating new therapeutic approaches is due to the lack of a complete understanding of the mechanisms of regulation of gene expression in this oncopathology. The study of micro-RNAs (short non-coding RNAs that regulate gene expression) can be the solution to both problems. The aim of the study was to analyze micro-RNA differential expression in the tumor and non-tumor tissues of CRC patients. Methods: 5 patients with CRC (colon adenocarcinoma, G2) were selected for the multiple parallel micro-RNA sequencing. The mirVana miRNA Isolation Kit protocol was used to isolate small RNA fractions. The miRNA library was prepared using the TruSeq Small RNASample Preparation Kit. Sequencing of the nucleotide sequences of cDNA libraries was performed using a MiSeq (Illumina, USA). The copy numbers of micro-RNA were determined by comparing the nucleotide sequence of the sequenced molecules in each sample with the known nucleotide sequences of micro-RNA presented in the databases. When analyzing the differential expression of micro-RNA, the DESeq2 method implemented in R medium was used. Results: Six differentially expressed micro-RNAs were detected (p < 0.05): 2 that decrease expression (hsa-miR-143-3p,hsa-miR-26a-5p) and 4 increase expression in the tumor relative to non-tumor (hsa-miR-25-3p, hsa-miR-92a-3p, hsa-miR-21-5p, hsa-let-7i-5p). The highest level of expression in both tumor and non-tumor tissue was observed for hsa-miR-143-3p, the lowest one for hsa-let-7i-5p. Moreover, the largest difference in micro-RNA expression in tumor tissue relative to non-tumor was shown for hsa-miR-92a-3p (4.5 times, p = 0.02), the smallest for hsa-miR-143-3p (2.4 times, p = 0.04). For miRNAs that differentially changed their expression, a search was made for target genes using the miRWalk 3.0 database. 14573 target genes were found, of which 3346 were for hypo-expressed micro-RNAs and 11228 for hyper-expressed micro-RNAs. Conclusions: Sequencing revealed 6 differentially expressed micro-RNAs (hsa-miR-143-3p, hsa-miR-26a-5p, hsa-miR-25-3p, hsa-miR-92a-3p, hsa-miR-21-5p, hsa-let-7i-5p) in the tumor tissue is relatively non-tumor tissues of the colon. The data obtained expand the understanding of the mechanisms of gene regulation in the context of this oncopathology and may possibly become the basis for highly specific tumor markers panel.

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