Serum exosomal miRNA from endometriosis patients correlates with disease severity

Abstract Purpose Exosomes are vesicles secreted by cells that contain a wide variety of biomolecules, including proteins or nucleic acids. MicroRNAs (miRNAs), which are commonly found in exosomes, are known to play important roles in the pathophysiology of endometriosis. Methods This study investigated the miRNA expression profile of serum exosomes from women with endometriosis in comparison with normal controls as well as the possible role of identified miRNAs in the pathogenesis of endometriosis. Exosomes with a diameter between 60 and 100 nm were identified by their expression of exosomal marker proteins CD9 and CD63. Results Microarray miRNA expression profiling analysis revealed that 26 genes were significantly up-regulated and 19 genes were significantly down-regulated in serum exosomes from endometriosis patients compared with normal controls. These differentially expressed miRNAs were mainly enriched in the regulation of cellular development, metabolism, and involved in the regulation of the MAPK and PI3k-Akt pathways. qRT-PCR analysis verified the differential expression of three miRNAs, miR-26b-5p, miR-215-5p, and miR-6795-3p. Conclusion Further analysis indicated that these differentially expressed miRNAs in serum exosomes may be involved in the pathogenesis of endometriosis and are related to the severity and certain symptoms of endometriosis.

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Identification of Differentially Expressed MicroRNAs in Osteosarcoma

Sarcoma ◽

10.1155/2011/732690 ◽

2011 ◽

Vol 2011 ◽

pp. 1-6 ◽

Cited By ~ 90

Author(s):

Rishi R. Lulla ◽

Fabricio F. Costa ◽

Jared M. Bischof ◽

Pauline M. Chou ◽

Maria de F. Bonaldo ◽

...

Keyword(s):

High Throughput ◽

Mirna Expression ◽

Expression Profiling ◽

Differentially Expressed ◽

Pcr Analysis ◽

Osteosarcoma Cell ◽

Human Osteoblasts ◽

Normal Human ◽

Mirna Expression Profiling

A limited number of reports have investigated the role of microRNAs in osteosarcoma. In this study, we performed miRNA expression profiling of osteosarcoma cell lines, tumor samples, and normal human osteoblasts. Twenty-two differentially expressed microRNAs were identified using high throughput real-time PCR analysis, and 4 (miR-135b, miR-150, miR-542-5p, and miR-652) were confirmed and validated in a different group of tumors. Both miR-135b and miR-150 have been previously shown to be important in cancer. We hypothesize that dysregulation of differentially expressed microRNAs may contribute to tumorigenesis. They might also represent molecular biomarkers or targets for drug development in osteosarcoma.

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MicroRNA expression patterns associated with hyperfunctioning and non-hyperfunctioning phenotypes in adrenocortical adenomas

Acta Endocrinologica ◽

10.1530/eje-13-0817 ◽

2014 ◽

Vol 170 (4) ◽

pp. 583-591 ◽

Cited By ~ 12

Author(s):

David Velázquez-Fernández ◽

Stefano Caramuta ◽

Deniz M Özata ◽

Ming Lu ◽

Anders Höög ◽

...

Keyword(s):

Mirna Expression ◽

Expression Profiles ◽

Expression Patterns ◽

Gene Mutations ◽

Mirna Expression Profile ◽

Differentially Expressed ◽

Adrenocortical Adenoma ◽

Tumor Subtypes ◽

Mirna Expression Profiles ◽

Differentially Expressed Mirnas

BackgroundThe adrenocortical adenoma (ACA) entity includes aldosterone-producing adenoma (APA), cortisol-producing adenoma (CPA), and non-hyperfunctioning adenoma (NHFA) phenotypes. While gene mutations and mRNA expression profiles have been partly characterized, less is known about the alterations involving microRNA (miRNA) expression.AimTo characterize miRNA expression profile in relation to the subtypes of ACAs.Subjects and methodsmiRNA expression profiles were determined in 26 ACAs (nine APAs, ten CPAs, and seven NHFAs) and four adrenal references using microarray-based screening. Significance analysis of microarrays (SAM) was carried out to identify differentially expressed miRNAs between ACA and adrenal cortices or between tumor subtypes. Selected differentially expressed miRNAs were validated in an extended series of 43 ACAs and ten adrenal references by quantitative RT-PCR.ResultsAn hierarchical clustering revealed separate clusters for APAs and CPAs, while the NHFAs were found spread out within the APA/CPA clusters. When NHFA was excluded, the clustering analysis showed a better separation between APA and CPA. SAM analysis identified 40 over-expressed and three under-expressed miRNAs in the adenomas as compared with adrenal references. Fourteen miRNAs were common among the three ACA subtypes. Furthermore, we found specific miRNAs associated with different tumor phenotypes.ConclusionThe results suggest that miRNA expression profiles can distinguish different subtypes of ACA, which may contribute to a deeper understanding of ACA development and potential therapeutics.

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miRNA Expression Profile and Effect of Wenxin Granule in Rats with Ligation-Induced Myocardial Infarction

International Journal of Genomics ◽

10.1155/2017/2175871 ◽

2017 ◽

Vol 2017 ◽

pp. 1-10 ◽

Cited By ~ 4

Author(s):

Aiming Wu ◽

Lixia Lou ◽

Jianying Zhai ◽

Dongmei Zhang ◽

Limin Chai ◽

...

Keyword(s):

Myocardial Infarction ◽

Expression Profile ◽

Mirna Expression ◽

Mirna Expression Profile ◽

Differentially Expressed ◽

Coronary Artery Ligation ◽

Mrna Levels ◽

Artery Ligation ◽

Gene Level ◽

Differentially Expressed Mirnas

Wenxin Granule (WXKL) is a traditional Chinese medicine used for treatment of myocardial infarction (MI) and arrhythmias. However, the genomic pathological mechanisms of MI and mechanisms of WXKL are largely unknown. This study aims to investigate a comprehensive miRNA expression profile, and the predicted correlation pathways to be targeted by differentially expressed miRNAs in MI, and mechanisms of WXKL from a gene level. MI rat model was established by a coronary artery ligation surgery. miRNA expression microarrays were performed and the data were deposited in Gene Expression Omnibus (GEO number GSE95855). And, pathway analysis was performed by using the DIANA-miRPath v3.0 online tool. The expressions of miR-1, miR-133, Cx43, and Cx45 were detected by quantitative real-time PCR. It was found that 35 differentially expressed miRNAs and 23 predicted pathways, including miR-1, miR-133, and gap junction pathway, are involved in the pathogenesis of MI. And, WXKL increased the expressions of miR-1 and miR-133, while also increased the mRNA levels of Cx43 and Cx45, and, especially, recovered the Cx43/Cx45 ratio near to normal level. The results suggest that regulatory effects on miR-1, miR-133, Cx43, and Cx45 might be a possible mechanism of WXKL in the treatment of MI at the gene level.

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miRNA Expression Profile of Saliva in Subjects of Yang Deficiency Constitution and Yin Deficiency Constitution

Cellular Physiology and Biochemistry ◽

10.1159/000493769 ◽

2018 ◽

Vol 49 (5) ◽

pp. 2088-2098 ◽

Cited By ~ 4

Author(s):

Yu Chen ◽

Yanling Wu ◽

Haiqiang Yao ◽

Hui Luo ◽

Bing Lin ◽

...

Keyword(s):

Expression Profile ◽

Mirna Expression ◽

Target Genes ◽

Mirna Expression Profile ◽

Differentially Expressed ◽

Hormone Signaling ◽

Chinese Han ◽

Cold Intolerance ◽

Yin Deficiency ◽

Differentially Expressed Mirnas

Background/Aims: Based on the theory of constitution in Traditional Chinese Medicine (TCM), the Chinese Han population has been classified into nine constitutions. Of these, Yang deficiency constitution mainly exhibit cold intolerance while Yin deficiency constitution mainly exhibit heat intolerance. Some studies have been carried out to explore the modern genetic and biological basis of such constitution classification, but more remains to be done. MicroRNA (miRNA) serves as post-transcriptional regulators of gene expression and may play a role in the classification process. Here, we examined miRNA expression profile of saliva to further improve the comprehensiveness of constitution classification. Methods: Saliva was collected from Chinese Han individuals with Yang deficiency, Yin deficiency and Balanced constitutions (n=5 each), and miRNA expression profile was determined using the Human miRNA OneArray®v7. Based on 1.5 Fold change, means log2|Ratio|≥0.585 and P-value< 0.05, differentially expressed miRNA was screened. Target genes were predicted using DIANA-TarBasev7.0 and analysis of KEGG pathway was carried out using DIANA-mirPathv.3. Results: We found that 81 and 98 differentially expressed miRNAs were screened in Yang deficiency and Yin deficiency constitution, respectively. Among them, 16 miRNAs were identical and the others were unique. In addition, the target genes that are regulated by the unique miRNAs were significantly enriched in 27 and 20 signaling pathways in Yang deficiency and Yin deficiency constitution, respectively. Thyroid hormone signaling pathway is present in both constitutions. These unique miRNAs that regulated target genes of thyroid hormone signaling pathway may be associated with cold intolerance or heat intolerance. Conclusion: The results of our study show that Yang deficiency and Yin deficiency constitutions exhibit systematic differences in miRNA expression profile. Moreover, the distinct characteristics of TCM constitution may be explained, in part, by differentially expressed miRNAs.

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Cardiac miRNA Expression and their mRNA Targets in a Rat Model of Prediabetes

International Journal of Molecular Sciences ◽

10.3390/ijms21062128 ◽

2020 ◽

Vol 21 (6) ◽

pp. 2128

Author(s):

Éva Sághy ◽

Imre Vörös ◽

Bence Ágg ◽

Bernadett Kiss ◽

Gábor Koncsos ◽

...

Keyword(s):

Zinc Finger ◽

Mirna Expression ◽

Drug Targets ◽

Zinc Finger Protein ◽

Target Prediction ◽

Mirna Expression Profile ◽

Differentially Expressed ◽

Small Rna Sequencing ◽

Mrna Targets ◽

Differentially Expressed Mirnas

Little is known about the mechanism of prediabetes-induced cardiac dysfunction. Therefore, we aimed to explore key molecular changes with transcriptomic and bioinformatics approaches in a prediabetes model showing heart failure with preserved ejection fraction phenotype. To induce prediabetes, Long-Evans rats were fed a high-fat diet for 21 weeks and treated with a single low-dose streptozotocin at week 4. Small RNA-sequencing, in silico microRNA (miRNA)-mRNA target prediction, Gene Ontology analysis, and target validation with qRT-PCR were performed in left ventricle samples. From the miRBase-annotated 752 mature miRNA sequences expression of 356 miRNAs was detectable. We identified two upregulated and three downregulated miRNAs in the prediabetic group. We predicted 445 mRNA targets of the five differentially expressed miRNAs and selected 11 mRNAs targeted by three differentially expressed miRNAs, out of which five mRNAs were selected for validation. Out of these five targets, downregulation of three mRNAs i.e., Juxtaposed with another zinc finger protein 1 (Jazf1); RAP2C, member of RAS oncogene family (Rap2c); and Zinc finger with KRAB and SCAN domains 1 (Zkscan1) were validated. This is the first demonstration that prediabetes alters cardiac miRNA expression profile. Predicted targets of differentially expressed miRNAs include Jazf1, Zkscan1, and Rap2c mRNAs. These transcriptomic changes may contribute to the diastolic dysfunction and may serve as drug targets.

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Comparative analysis of relative gene expression data reveals novel microRNAs in the artery of rats with renovascular hypertension

Archives of Biological Sciences ◽

10.2298/abs200905047y ◽

2020 ◽

Vol 72 (4) ◽

pp. 535-541

Author(s):

Hui Yu ◽

Hai Hu ◽

Zhanli Wang

Keyword(s):

Renovascular Hypertension ◽

Mirna Expression ◽

Molecular Mechanisms ◽

Vascular Dysfunction ◽

Differentially Expressed ◽

Vascular Endothelial ◽

Differentially Expressed Mirnas ◽

Mirna Expression Profiling ◽

Generation Sequencing ◽

Relative Gene

Hypertension is associated with impaired vascular endothelial function. However, the regulatory mechanisms of vascular dysfunction in rats with renovascular hypertension (RVH) remain poorly understood. In this study, the 2-kidney- 1-clip (2K1C) hypertensive rat model was utilized. Next-generation sequencing was then used to detect microRNA (miRNA) expression profiling in the arteries of 2K1C rats. We identified 17 miRNAs that were differentially expressed in the 2K1C group compared with the sham group, of which 9 were downregulated and 8 were upregulated. These differentially expressed miRNAs were found to be associated with immune/inflammatory and metabolic pathways, which are involved in vascular dysfunction. Treatment with losartan maintained the expression of the differentially expressed miRNAs, miR-31a-5p and miR-142-3p, and the levels of TNF-?, IL-1?, IL-6 and MCP-1, indicating that the differentially expressed miRNAs and their associated immune/inflammatory pathways play a pivotal role in the modulation of the vascular dysfunction in 2K1C rats. Our study provides valuable information about miRNA expression in the arteries of 2K1C rats, expanding our understanding of the complex molecular mechanisms underlying the vascular dysfunction in rats with RVH.

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Exosomal miRNA profiling from H5N1 avian influenza virus-infected chickens

Veterinary Research ◽

10.1186/s13567-021-00892-3 ◽

2021 ◽

Vol 52 (1) ◽

Author(s):

Yeojin Hong ◽

Anh Duc Truong ◽

Jiae Lee ◽

Thi Hao Vu ◽

Sooyeon Lee ◽

...

Keyword(s):

Influenza Virus ◽

Avian Influenza ◽

Avian Influenza Virus ◽

Mirna Expression ◽

Expression Patterns ◽

Differentially Expressed ◽

Small Rna Sequencing ◽

Sequencing Data ◽

Differentially Expressed Mirnas ◽

Exosomal Mirna

AbstractExosomes are membrane vesicles containing proteins, lipids, DNA, mRNA, and micro RNA (miRNA). Exosomal miRNA from donor cells can regulate the gene expression of recipient cells. Here, Ri chickens were divided into resistant (Mx/A; BF2/B21) and susceptible (Mx/G; BF2/B13) trait by genotyping of Mx and BF2 genes. Then, Ri chickens were infected with H5N1, a highly pathogenic avian influenza virus (HPAIV). Exosomes were purified from blood serum of resistant chickens for small RNA sequencing. Sequencing data were analysed using FastQCv0.11.7, Cutadapt 1.16, miRBase v21, non-coding RNA database, RNAcentral 10.0, and miRDeep2. Differentially expressed miRNAs were determined using statistical methods, including fold-change, exactTest using edgeR, and hierarchical clustering. Target genes were predicted using miRDB. Gene ontology analysis was performed using gProfiler. Twenty miRNAs showed significantly different expression patterns between resistant control and infected chickens. Nine miRNAs were up-regulated and 11 miRNAs were down-regulated in the infected chickens compared with that in the control chickens. In target gene analysis, various immune-related genes, such as cytokines, chemokines, and signalling molecules, were detected. In particular, mitogen-activated protein kinase (MAPK) pathway molecules were highly controlled by differentially expressed miRNAs. The result of qRT-PCR for miRNAs was identical with sequencing data and miRNA expression level was higher in resistant than susceptible chickens. This study will help to better understand the host immune response, particularly exosomal miRNA expression against HPAIV H5N1 and could help to determine biomarkers for disease resistance.

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P-117 Pre-selected for an award: Bioinformatic analysis of NRF2 in the study of association of NRF2 variant and male infertility related to smoking status

Human Reproduction ◽

10.1093/humrep/deab127.044 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

D Aydos ◽

O S Aydos ◽

Y Yukselten ◽

A Sunguroglu ◽

K Aydos

Keyword(s):

Dna Damage ◽

Male Infertility ◽

Mirna Expression ◽

Smoking Status ◽

Differentially Expressed ◽

Control Group ◽

Functional Variants ◽

Significant Difference ◽

Differentially Expressed Mirnas

Abstract Study question Could Nrf2 polymorphism (-617C>A; rs6721961) and oxidative stress (OS)-induced changes of signature seminal plasma (SP) miRNAs related to Nrf2 provide possible biomarkers of male infertility? Summary answer -617C>A SNP is associated with infertility through sperm OS DNA damage and miR-582-5p and miR-20a-5p, differentially represented between spermatozoa of smokers-non-smokers, might regulate Nrf2/ARE axis. What is known already As an extrinsic factor causing OS, smoking decreases male infertility by causing sperm membrane damage and DNA fragmentation. Expression of proteins related to the antioxidant defense system and phase 2 detoxifying enzymes controlled mainly by Nrf2/ARE pathway components is vital in managing OS-induced DNA damage. miRNAs, which multiple of are produced abundantly in male germ cells throughout spermatogenesis, have been detected in SP and contribute to multiple biological processes related to male reproductive events. miRNA-expression alterations may be induced in response to OS and without involving DNA sequence changes, miRNAs can provide additional mechanism of regulating the Nrf2 gene expression. Study design, size, duration Wild-type (WT) and SNP (-617) alleles in the Nrf2 gene were studied in 100 infertile cases and 100 controls and their associations with seminal parameters in relation to smoking status were assessed. In infertile cases, sperm DNA damage level was determined and compared among Nrf2 genotypes. Interactions between differentially expressed miRNAs (DEMIs) in response to smoking and Nrf2/ARE pathway components were visualized on a miRNA-mRNA regulatory network using CluePedia (v1.5.7) plugin of Cytoscape software (v3.8.2). Participants/materials, setting, methods Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was utilized to genotype the Nrf2 SNP (-617). DNA damages were analyzed by Comet assay. DEMIs were identified by a comprehensive bioinformatics analysis using the miRNA expression dataset GSE44134 downloaded from the GEO database. Predicted targets of DEMIs in smokers were identified by mirDIP portal. Known interactions between Nrf2 and its first neighbors were visualized after selecting STRING-actions, miRTarBase and miRecords validated miRNA source files from CluePedia panel. Main results and the role of chance There was significant difference for Nrf2 polymorphism between fertile and infertile males. The A allele was detected more frequently in the patient group; (P = 0.001). The frequencies of the C and A alleles of the Nrf2 were 62% and 38% in patients, and 78% and 44% in control group. The AA genotype was higher in the infertiles; 14% vs. 3% (P = 0.001). In smokers, sperm quality decreased significantly in AA genotype. The risk of DNA damage was highest with 224.58 AU in the AA genotype group, whereas it is the lowest with 164.56 AU in those carrying the CC genotype (P < 0.005). 21 differentially expressed miRNAs (including 7 downregulated and 14 upregulated in smokers) were identified. Among the upregulated DEMIs, miR-582-5p, miR-20a-5p, miR-573, miR-186-5p, miR-499a-5p were found to target the Nrf2 mRNA, suggesting their usage as biomarkers capable of indicating the antioxidant ability of the male reproductive system. The interrelations between Nrf2/Nrf2 direct interactors and DEMIs revealed the regulatory role of hsa-miR-20a-5p in SQSTM1/p62-Keap1-Nrf2 axis linked to selective autophagy. hsa-miR-582-5p was found to regulate the JNK/Jun/caspase-3 pathway, previously shown to be activated in response to OS, in which JUN can activate or suppress the Nrf2 expression. Limitations, reasons for caution Small number of cases while evaluating the effect of smoking weakens our ability to generalize the results. Including other coexisting factors and larger patient groups carrying other functional variants of Nrf2 as well as confirming the results at the protein level would further strengthen the results of the study. Wider implications of the findings This study is the first to report -617C>A polymorphism in the Nrf2 gene in the Turkish population and such a SNP may cause impaired fertility in men, especially in smokers, through oxidative metabolism. Considering these data may be valuable in determining risk groups. Trial registration number N/A

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MicroRNA expression signatures of atrial fibrillation: The critical systematic review and bioinformatics analysis

Experimental Biology and Medicine ◽

10.1177/1535370219890303 ◽

2019 ◽

Vol 245 (1) ◽

pp. 42-53 ◽

Cited By ~ 2

Author(s):

Nan-Nan Shen ◽

Chi Zhang ◽

Zheng Li ◽

Ling-Cong Kong ◽

Xin-Hua Wang ◽

...

Keyword(s):

Atrial Fibrillation ◽

Systematic Review ◽

Sensitivity Analysis ◽

Mirna Expression ◽

Bioinformatics Analysis ◽

Detection Method ◽

Expression Profiles ◽

Differentially Expressed ◽

Cochrane Library ◽

Differentially Expressed Mirnas

Association between microRNA (miRNA) expression signatures and atrial fibrillation has been evaluated with inconsistent findings in different studies. This study aims to identify miRNAs that actually play vital role in pathophysiological process of atrial fibrillation and explore miRNA-targeted genes and the involved pathways. Relevant studies were retrieved from the electronic databases of Embase, Medline, and Cochrane Library to determine the miRNA expression profiles between atrial fibrillation subjects and non-atrial fibrillation controls. Robustness of results was assessed using sensitivity analysis. Subgroup analyses were performed based on species, miRNA detection method, sample source, and ethnicity. Quality assessment of studies was independently conducted according to QUADAS-2. Bioinformatics analysis was applied to explore the potential genes and pathways associated with atrial fibrillation, which were targeted by differentially expressed miRNAs. Form of pooled results was shown as log10 odds ratios (logORs) with 95% confidence intervals (CI), and random-effects model was used. In total, 40 articles involving 283 differentially expressed miRNAs were reported. And 51 significantly dysregulated miRNAs were identified in consistent direction, with 22 upregulated and 29 downregulated. Among above-mentioned miRNAs, miR-223-3p (logOR 6.473; P < 0.001) was the most upregulated, while miR-1-5p (logOR 7.290; P < 0.001) was the most downregulated. Subgroup analysis confirmed 53 significantly dysregulated miRNAs (21 upregulated and 32 downregulated) in cardiac tissue, with miRNA-1-5p and miRNA-223-3p being the most upregulated and downregulated miRNAs, respectively. Additionally, miR-328 and miR-1-5p were highly blood-specific, and miR-133 was animal-specific. In the detection method sub-groups, miRNA-29b and miRNA-223-3p were differentially expressed consistently. Four miRNAs, including miRNA-223-3p, miRNA-21, miRNA-328, and miRNA-1-5p, were consistently dysregulated in both Asian and non-Asian. Results of sensitivity analysis showed that 47 out of 51 (92.16%) miRNAs were dysregulated consistently. Totally, 51 consistently dysregulated miRNAs associated with atrial fibrillation were confirmed in this study. Five important miRNAs, including miR-29b, miR-328, miR-1-5p, miR-21, and miR-223-3p may act as potential biomarkers for atrial fibrillation. Impact statement Atrial fibrillation (AF) is considered as the most common arrhythmia, and it subsequently causes serious complications including thrombosis and heart failure that increase the social burden. The definite mechanisms underlying AF pathogenesis remain complicated and unclear. Many studies attempted to discover the transcriptomic changes using microarray technologies, and the present studies for this hot topic have assessed individual miRNAs profiles for AF. However, results of different articles are controversial and not each reported miRNA is actually associated with the pathogenesis of AF. The present systematic review and meta-analysis identified that 51 consistently dysregulated miRNAs were associated with AF. Of these miRNAs, five miRNAs (miRNA-1-5p, miRNA-328, miRNA-29b, miRNA-21, and miRNA-223-3p) may act as novel biomarkers for AF. The findings could offer a better description of the biological characteristics of miRNAs, meanwhile might serve as new target for the intervention and monitoring AF in future studies.

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Analysis of microRNA Patterns in Hodgkin’s Lymphoma (HL).

Blood ◽

10.1182/blood.v108.11.474.474 ◽

2006 ◽

Vol 108 (11) ◽

pp. 474-474

Author(s):

Alfons Navarro ◽

Anna Gaya ◽

Aina Pons ◽

Pau Abrisqueta ◽

Bernat Gel ◽

...

Keyword(s):

Lymph Nodes ◽

Mirna Expression ◽

Cellular Proliferation ◽

Clinical Stage ◽

Expression Patterns ◽

Differentially Expressed ◽

Apoptotic Pathway ◽

Apoptosis Pathway ◽

Differentially Expressed Mirnas ◽

Clinical Stages

Abstract Mature microRNAs (miRNA) are recently discovered small RNA molecules of 21–25 nucleotides in length. They act as negative regulators of expression of important genes like those participating in cellular proliferation or apoptosis. There is evidence that miRNA play an important role in carcinogenesis. The objective of this study was to compare the miRNA expression patterns in normal lymph nodes and in lymph nodes from patients with HL. Moreover, we investigated the miRNA pattern of HL depending on Epstein-Barr Virus (EBV) expression. We assessed 156 mature miRNAs by Stem-loop RT-PCR and Real time PCR in ABI PRISM 7500 in 9 normal lymph nodes and 39 patients diagnosed with HL nodular sclerosis subtype (15 EBV+ and 24 EBV-)at a single institution. Patients median age was 27 years (range, 15–52), and clinical stage was I (n=1); II (n=22); III (n=8) and IV (n=8); 41% of the patients reported B symptoms. RNA was obtained in all cases from formalin fixed paraffin embedded tissues. miRNA expression data was normalized to let-7a miRNA and to global median. Relative quantification of miRNA expression was calculated with the 2−ΔΔCt method. The data were presented as log10 of relative quantity of target miRNA. Normal human lymph node tissue was used as calibrator for all samples. Data were analyzed by means of Significant Analysis of Microarrays (SAM), Student’s t-test (with random variance model) and Class prediction methods using BRB Array Tools version 3.4.0 and TIGR Multiexperiment Viewer version 3.1. Of the 156 miRNAs analyzed, 35 were differentially expressed between normal lymph nodes and HL (12 miRNAs were upregulated and 23 downregulated). The most differentially overexpressed miRNAs was miR-216, which inhibits apoptosis pathway. Other differentially expressed miRNAs were miR-140, 204, 19a, 20, 191 and 142-3p, which have been associated to the genesis of hematological and non-hematological malignances. With respect to EBV+ vs. EBV− cases, we found that miR-96 and miR-335 were underexpressed in the EBV+ cases as compared to EBV− (p=0.001). These miRNAs have RNF34 and BIRC2 genes as targets, which have an antiapoptotic function. We also found that miR-138 was more frequently overexpressed in clinical stages I–II versus clinical stages III–IV (p=0.004), and that miR-328 was more frequently overexpressed in stages III–IV (p=0.004). In conclusion, miRNAs might have a role in the pathogenesis of HL. The miRNA pattern is different between the EBV+ and EBV− cases, and the differentially expressed miRNAs seems to be related to the apoptotic pathway.

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