• acute myeloid leukemia
• chemoresistance
• microRNAs

• Humans
• Leukemia, Myeloid, Acute/genetics
• Leukemia, Myeloid, Acute/metabolism
• Leukemia, Myeloid, Acute/drug therapy
• Leukemia, Myeloid, Acute/pathology
• MicroRNAs/genetics
• Signal Transduction/genetics
• Forkhead Box Protein O1/genetics
• Forkhead Box Protein O1/metabolism
• Cell Cycle Proteins/genetics
• Cell Cycle Proteins/metabolism
• Female
• Nuclear Proteins/genetics
• Nuclear Proteins/metabolism
• Male
• Up-Regulation
• Gene Expression Regulation, Leukemic
• Middle Aged
• Adult
• Gene Expression Profiling/methods
• GADD45 Proteins
• Superoxide Dismutase

• DJCLS 04FN/2019 Jose-Carreras-Leukemia-Foundation

• Diabetes
• EMT and MET processes
• Liver diseases
• MRNA-miRNA signature
• MiR-26a-5p
• N-cadherin

• Humans
• Epithelial-Mesenchymal Transition/genetics
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Diabetes Mellitus, Type 2/genetics
• Diabetes Mellitus, Type 2/metabolism
• Diabetes Mellitus, Type 2/pathology
• Diabetes Mellitus, Type 2/complications
• Liver Neoplasms/genetics
• Liver Neoplasms/pathology
• Liver Neoplasms/metabolism
• Carcinoma, Hepatocellular/genetics
• Carcinoma, Hepatocellular/pathology
• Carcinoma, Hepatocellular/metabolism
• RNA, Messenger/genetics
• RNA, Messenger/metabolism
• Non-alcoholic Fatty Liver Disease/genetics
• Non-alcoholic Fatty Liver Disease/pathology
• Non-alcoholic Fatty Liver Disease/metabolism
• Disease Progression
• Male
• Computational Biology/methods

• 629PED/2022 CCCDI-UEFISCDI, project number PN-III-P2-2.1-PED-2021-3180, within PNCDI III
• 629PED/2022 CCCDI-UEFISCDI, project number PN-III-P2-2.1-PED-2021-3180, within PNCDI III
• 629PED/2022 CCCDI-UEFISCDI, project number PN-III-P2-2.1-PED-2021-3180, within PNCDI III
• 629PED/2022 CCCDI-UEFISCDI, project number PN-III-P2-2.1-PED-2021-3180, within PNCDI III
• 629PED/2022 CCCDI-UEFISCDI, project number PN-III-P2-2.1-PED-2021-3180, within PNCDI III
• 629PED/2022 CCCDI-UEFISCDI, project number PN-III-P2-2.1-PED-2021-3180, within PNCDI III
• 629PED/2022 CCCDI-UEFISCDI, project number PN-III-P2-2.1-PED-2021-3180, within PNCDI III
• 28571/02.10.2023 UMFCD

• Biomarkers
• Drug resistance
• Epigenetic regulation
• Epithelial-mesenchymal transition
• MicroRNA
• Ovarian cancer

• Female
• Humans
• Carboplatin/pharmacology
• Prognosis
• Ovarian Neoplasms/drug therapy
• Ovarian Neoplasms/genetics
• Phenotype

MicroRNAs (miRNAs) play a vital role in improving meat quality by binding to messenger RNAs (mRNAs). We performed an integrated analysis of miRNA and mRNA expression profiling between bulls and steers based on the differences in meat quality traits. Fat and fatty acids are the major phenotypic indices of meat quality traits to estimate between-group variance. In the present study, 90 differentially expressed mRNAs (DEGs) and 18 differentially expressed miRNAs (DEMs) were identified. Eighty-three potential DEG targets and 18 DEMs were used to structure a negative interaction network, and 75 matching target genes were shown in this network. Twenty-six target genes were designated as intersection genes, screened from 18 DEMs, and overlapped with the DEGs. Seventeen of these genes enriched to 19 terms involved in lipid metabolism. Subsequently, 13 DEGs and nine DEMs were validated using quantitative real-time PCR, and seven critical genes were selected to explore the influence of fat and fatty acids through hub genes and predict functional association. A dual-luciferase reporter and Western blot assays confirmed a predicted miRNA target (bta-miR-409a and PLIN5). These findings provide substantial evidence for molecular genetic controls and interaction among genes in cattle.

• MicroRNAs
• Regulatory
• Stem cells
• Viruses

• apoptosis
• cell cycle
• lung cancer
• miR-330
• migration

Purpose: Based on WHO report, colorectal cancer (CRC) is the second cause of death among patients with cancer worldwide. Dysregulation of miRNAs expressions has been demonstrated in different human cancers, especially CRC. Studies have shown that miR-330 could act as both TS-miR and/or oncomiR in different types of cancers. BACH1 is also identified as a transcription factor, which is involved in ontogenesis. In this study, we evaluated the CRC suppression via silencing of BACH1 by small silencer molecule called miR-330.

Methods: Firstly, we analyzed the BACH1, miR-330-3p and miR-330-5p expressions according to the colon adenocarcinoma (COAD) and rectal adenocarcinoma (READ) project established from a patient of the colon and rectal cancer patients in The Cancer Genome Atlas (TCGA) database. The targeting of BACH1 via miR-330 in human CRC cells was evaluated by Vejnar bioinformatics methods, and confirmed by qRT-PCR and western blot analysis. Proliferation was performed by MTT assay. The MMP9, CXCR4, and VEGFR proteins were measured by western blotting.

Results: The analysis of BACH1, miR-330-3p, and miR-330-5p expressions according to the COAD and READ projects showed that BACH1 was overexpressed, but miR-330-3p and miR330-5p were reduced in CRC tumors compared to normal controls. The miR-330 induction prevented proliferation of CRC cell by targeting BACH1 mRNA, which represses MMP9, C-X-C chemokine receptor type 4 (CXCR4), and vascular endothelial growth factor receptor (VEGFR) proteins expressions.

Conclusion: Our results suggested that BACH1 is a potential target for miR-330 in CRC cells. The miR-330 induction inhibits CRC cells proliferation by suppressing BACH1 expression in posttranscriptional level. It was suggested that targeting of BACH1 via miRNA such as miR-330 could be a valid strategy in the field of CRC targeted therapy via modulating the oncogenic signaling pathway.

• BACH1
• CXCR4
• Colorectal cancer
• MMP9
• Proliferation
• VEGFR
• miR-330

• ATP
• hydrogen sulfide
• mitochondria
• trisomy

• Cell Proliferation
• Child
• Child, Preschool
• Cysteine/analogs & derivatives
• Cysteine/metabolism
• Down Syndrome/metabolism
• Down Syndrome/pathology
• Energy Metabolism
• Female
• Fibroblasts/metabolism
• Fibroblasts/pathology
• Humans
• Hydrogen Sulfide/metabolism
• Infant
• Infant, Newborn
• Male
• Mitochondria/metabolism
• Oxidative Phosphorylation
• Sulfurtransferases/antagonists & inhibitors
• Sulfurtransferases/metabolism

• Animal free research
• Beta cells
• Type 2 diabetes
• miRNA
• ncRNA regulation

• Animal model
• Brain
• Neurocognitive disorders
• POCD
• miR-190a

• Biomarker
• Depression
• Ischemia
• Stroke
• microRNA

Rapid changes in the expression of many messenger RNA (mRNA) species follow exposure of cells to ionizing radiation. One of the hypothetical mechanisms of this response may include microRNA (miRNA) regulation, since the amounts of miRNAs in cells also vary upon irradiation. To address this possibility, we designed experiments using cancer-derived cell lines transfected with luciferase reporter gene containing sequences targeted by different miRNA species in its 3′- untranslated region. We focus on the early time-course response (1 h past irradiation) to eliminate secondary mRNA expression waves.

Experiments revealed that the irradiation-induced changes in the mRNA expression depend on the miRNAs which interact with mRNA. To identify the strongest interactions, we propose a mathematical model which predicts the mRNA fold expression changes, caused by perturbation of microRNA-mRNA interactions. Model was applied to experimental data including various cell lines, irradiation doses and observation times, both ours and literature-based. Comparison of modelled and experimental mRNA expression levels given miRNA level changes allows estimating how many and which miRNAs play a significant role in transcriptome response to stress conditions in different cell types. As an example, in the human melanoma cell line the comparison suggests that, globally, a major part of the irradiation-induced changes of mRNA expression can be explained by perturbed miRNA-mRNA interactions. A subset of about 30 out of a few hundred miRNAs expressed in these cells appears to account for the changes. These miRNAs play crucial roles in regulatory mechanisms observed after irradiation. In addition, these miRNAs have a higher average content of GC and a higher number of targeted transcripts, and many have been reported to play a role in the development of cancer.

Our proposed mathematical modeling approach may be used to identify miRNAs which participate in responses of cells to ionizing radiation, and other stress factors such as extremes of temperature, exposure to toxins, and drugs.

The online version of this article (10.1186/s12864-019-5464-0) contains supplementary material, which is available to authorized users.

• ionizing radiation
• miRNA
• miRNA-mRNA interactions
• stressing factor

• ISG20
• antiviral immunity
• influenza A virus
• lnc-ISG20
• lnc-RNA
• miR-326

• biomarker
• chemotherapy
• disease-free survival rate
• miR-125a-3p
• non-small cell lung cancer
• overall survival rate
• prognosis

• Biomarkers, Tumor/genetics
• Blood Platelets
• Cell-Free Nucleic Acids/analysis
• Cell-Free Nucleic Acids/isolation & purification
• Diet
• Exercise
• Female
• Genetic Markers
• High-Throughput Nucleotide Sequencing/methods
• High-Throughput Nucleotide Sequencing/standards
• Humans
• Male
• MicroRNAs/genetics
• Polymerase Chain Reaction/methods
• Polymerase Chain Reaction/standards
• Specimen Handling/standards
• Time Factors

• U01 HL126496 NHLBI NIH HHS

Previous studies have suggested that dysregulation of microRNA (miR) −124a is associated with various types of human cancer. However, there are few studies reporting the level of miR-124a expression in non-small cell lung cancer (NSCLC). The present study investigated the association between miR-124a and NSCLC by analyzing the differential expression of miR-124a in NSCLC using the GEO database, as well as subsequently performing reverse transcription-quantitative polymerase chain reaction analysis on 160 NSCLC biopsies, 32 of which were paired with adjacent normal tissues. The results indicated that mir-124a expression levels were decreased in NSCLC tumor biopsies compared with adjacent normal tissues. The overall survival (OS) in patients with a high expression of miR-124a was prolonged relative to patients with low expression of miR-124a. The expression levels of miR-124a were associated with clinical characteristics, including lymph-node metastasis, tumor differentiation, tumor node metastasis (TNM) stage and diameter. Frequently, lymph-node metastasis, TNM stage, diameter and lack of chemotherapy have been associated with a worse prognosis in patients. In addition, the present study identified that high expression of miR-124awith chemotherapy may increase OS. In conclusion, the current study demonstrated that miR-124a was downregulated in NSCLC, and miR-124a was a potential prognostic tumor biomarker response to chemotherapy.

• MicroRNA
• medium reiteration frequency transposon
• palindromic structure
• thoroughbred horse

• Adrenal Glands/physiology
• Animals
• Cerebellum/physiology
• DNA Transposable Elements/genetics
• Duodenum/physiology
• Gene Expression Regulation
• Genome
• Horses/genetics
• Humans
• Introns
• Inverted Repeat Sequences/genetics
• Lung/physiology
• MicroRNAs/genetics
• MicroRNAs/metabolism
• RNA Precursors/genetics
• RNA Precursors/metabolism
• Spleen/physiology

Endemic Burkitt lymphoma (eBL) is an aggressive B cell lymphoma and is associated with Epstein-Barr virus (EBV) and Plasmodium falciparum malaria co-infections. Central to BL oncogenesis is the over-expression of the MYC proto-oncogene which is caused by a translocation of an Ig enhancer in approximation to the myc gene. While whole genome/transcriptome sequencing methods have been used to define driver mutations and transcriptional dysregulation, microRNA (miRNA) dysregulation and differential expression has yet to be fully characterized. We hypothesized that both human and EBV miRNAs contribute to eBL clinical presentation, disease progression, and poor outcomes. Using sensitive and precise deep sequencing, we identified miRNAs from 17 Kenyan eBL patient tumor samples and delineated the complement of both host and EBV miRNAs. One human miRNA, hsa-miR-10a-5p was found to be differentially expressed (DE), being down-regulated in jaw tumors relative to abdominal and in non-survivors compared to survivors. We also examined EBV miRNAs, which made up 2.7% of the miRNA composition in the eBL samples. However, we did not find any significant associations regarding initial patient outcome or anatomical presentation. Gene ontology analysis and pathway enrichment of previously validated targets of miR-10a-5p suggest that it can promote tumor cell survival as well as aid in evasion of apoptosis. To examine miR-10a-5p regulatory effect on gene expression in eBL, we performed a pairwise correlation coefficient analysis on the expression levels of all its validated targets. We found a significant enrichment of correlated target genes consistent with miR-10a-5p impacting expression. The functions of genes and their correlation fit with multiple target genes impacting tumor resilience. The observed downregulation of miR-10a and associated genes suggests a role for miRNA in eBL patient outcomes and has potential as a predictive biomarker that warrants further investigation.

• EBV
• RNAseq
• endemic Burkitt lymphoma
• miR-10a-5p
• microRNA expression

• Adhesion
• Adhesion motifs
• Biomimetic polymers
• Mesenchymal stem cells
• Microenvironment

• MiRNAs prediction
• Misgurnus anguillicaudatus
• Molecular cloning and expression
• Vascular endothelial growth factor A

• cryobiology
• hibernation
• metabolic depression
• noncoding RNAs
• stress resistance

Evidence is mounting that circadian disruption (CD) is a potential carcinogen in breast cancer development. However, despite the growing concern, to our knowledge, no studies have attempted a genome-wide analysis of CD-induced gene expression changes in mammary tissues. Using a rodent model system, a proven photoperiod-shifting paradigm, varying degrees of CD, and Illumina sequencing, we performed an exploratory genome-wide mRNA analysis in mammary tissues. Even though our analysis did not identify any significant patterns in mRNA levels based on the degree of CD, and the majority of groups did not show changes in gene expression on a large-scale, one group (two-week chronic ZT19) displayed 196 differentially expressed genes, 51 of which have been linked to breast cancer. Through gene-specific pathway analysis, the data illustrate that CD may promote breast cancer development through downregulation of DNA repair and p53 signaling pathways, thus promoting genomic instability and cancer development. Although these results have to be interpreted with caution because only a single group illustrated drastic changes in transcript levels, they indicate that chronic CD may directly induce changes in gene expression on a large-scale with potentially malignant consequences.

• breast cancer
• circadian disruption
• transcriptome

MicroRNAs (miRNAs) play a vital role in muscle development by binding to messenger RNAs (mRNAs). Based on prenatal skeletal muscle at 33, 65 and 90 days post-coitus (dpc) from Landrace, Tongcheng and Wuzhishan pigs, we carried out integrated analysis of miRNA and mRNA expression profiling. We identified 33, 18 and 67 differentially expressed miRNAs and 290, 91 and 502 mRNA targets in Landrace, Tongcheng and Wuzhishan pigs, respectively. Subsequently, 12 mRNAs and 3 miRNAs differentially expressed were validated using quantitative real-time PCR (qPCR), and 5 predicted miRNA targets were confirmed via dual luciferase reporter or western blot assays. We identified a set of miRNAs and mRNA genes differentially expressed in muscle development. Gene ontology (GO) enrichment analysis suggests that the miRNA targets are primarily involved in muscle contraction, muscle development and negative regulation of cell proliferation. Our data indicated that more mRNAs are regulated by miRNAs at earlier stages than at later stages of muscle development. Landrace and Tongcheng pigs also had longer phases of myoblast proliferation than Wuzhishan pigs. This study will be helpful to further explore miRNA-mRNA interactions in myogenesis and aid to uncover the molecular mechanisms of muscle development and phenotype variance in pigs.

• mRNA
• microRNA
• myocardial infarction
• sequencing

• Bladder cancer
• Correlation
• MicroRNA
• Target prediction
• The Cancer Genome Atlas
• mRNA

We previously demonstrated an inverse correlation between tyrosinase-related protein 1 (TYRP1) mRNA expression in melanoma metastases and patient survival. However, TYRP1 protein was not detected in half of tissues expressing mRNA and did not correlate with survival. Based on a study reporting that 3′ untranslated region (UTR) of TYRP1 mRNA contains two miR-155-5p (named miR-155) binding sites exhibiting single-nucleotide polymorphisms (SNPs) that promote (matched miRNA–mRNA interaction) mRNA decay or not (mismatched), we aimed to investigate the role of miR-155 in the regulation of TYRP1 mRNA expression and protein translation accounting for these SNPs.

The effect of miR-155 on TYRP1 mRNA/protein expression was evaluated in two melanoma cell lines harbouring matched or mismatched miR-155–TYRP1 mRNA interaction after transfection with pre-miR-155. In parallel, 192 skin and lymph node melanoma metastases were examined for TYRP1 mRNA/protein, miR-155 and SNPs and correlated with patient survival. TYRP1 mRNA, SNPs at its 3′UTR and miR-155 were analysed by RT–qPCR, whereas TYRP1 protein was evaluated by western blot in cell lines and by immunohistochemistry in metastatic tissues.

The miR-155 induced a dose-dependent TYRP1 mRNA decay and hampered its translation into protein in the line with the ‘match' genotype. In melanoma metastases, TYRP1 mRNA inversely correlated with miR-155 expression but not with TYRP1 protein in the ‘match' group, whereas it positively correlated with protein but not with miR-155 in the ‘mismatch' group. Consequently, in the latter group, TYRP1 protein inversely correlated with survival.

Polymorphisms in 3′UTR of TYRP1 mRNA can affect TYRP1 mRNA regulation by miR-155 and its subsequent translation into protein. These SNPs can render TYRP1 mRNA and protein expression nonsusceptible to miR-155 activity and disclose a prognostic value for TYRP1 protein in a subgroup of melanoma patients. These data support the interest in the prognostic value of melanogenic markers and propose TYRP1 to refine prognosis in patients with advanced disease.

Ulcerative colitis (UC) is associated with differential colonic expression of genes involved in immune response (e.g. IL8) and barrier integrity (e.g. cadherins). MicroRNAs (miRNAs) are regulators of gene expression and are involved in various immune-related diseases. In this study, we investigated (1) if miRNA expression in UC mucosa is altered and (2) if any of these changes correlate with mucosal mRNA expression. Integration of mRNA and miRNA expression profiling may allow the identification of functional links between dysregulated miRNAs and their target mRNA.

Colonic mucosal biopsies were obtained from 17 UC (10 active and 7 inactive) patients and 10 normal controls. Total RNA was used to analyze miRNA and mRNA expression via Affymetrix miRNA 2.0 and Affymetrix Human Gene 1.0ST arrays, respectively. Both miRNA and gene expression profiles were integrated by correlation analysis to identify dysregulated miRNAs with their corresponding predicted target mRNA. Microarray data were validated with qRT-PCR. Regulation of IL8 and CDH11 expression by hsa-miR-200c-3p was determined by luciferase reporter assays.

When comparing active UC patients vs. controls, 51 miRNAs and 1543 gene probe sets gave significantly different signals. In contrast, in inactive UC vs. controls, no significant miRNA expression differences were found while 155 gene probe sets had significantly different signals. We then identified potential target genes of the significantly dysregulated miRNAs and genes in active UC vs. controls and found a highly significant inverse correlation between hsa-miR-200c-3p and IL8, an inflammatory marker, and between hsa-miR-200c-3p and CDH11, a gene related to intestinal epithelial barrier function. We could demonstrate that hsa-miR-200c-3p directly regulates IL8 and CDH11 expression.

Differential expression of immune- and barrier-related genes in inflamed UC mucosa may be influenced by altered expression of miRNAs. Integrated analysis of miRNA and mRNA expression profiles revealed hsa-miR-200c-3p for use of miRNA mimics as therapeutics.

• differentiation
• miRNA
• satellite cells
• skeletal muscle
• transcriptome

MicroRNAs (miRNAs) are endogenous small non-coding RNAs of ~23 nucleotides in length that form up a novel class of regulatory determinants, with a large set of target mRNAs postulated for every single miRNA. Thousands of miRNAs have been discovered so far, with hundreds of them shown to govern biological processes with impact on disease. However, very little is known about how they specifically interfere with biological pathways and disease mechanisms. To investigate this interaction, the hunt for direct miRNA targets that mediate the miRNA effects—the “needle in the haystack”—is an essential step. In this review we provide a comprehensive workflow of successfully applied methods starting from the identification of putative miRNA-target pairs, followed by validation of direct miRNA–mRNA interactions, and finally presenting methods that dissect the impact of particular miRNA-target pairs on a biological process or disease. This guide allows the way to be paved for obtaining biologically meaningful miRNA targets.

• Cell reprograming
• MicroRNA
• STEM cell

• Cell Dedifferentiation/genetics
• Cell Differentiation/genetics
• Cellular Reprogramming/genetics
• Embryonic Stem Cells/metabolism
• Gene Expression Profiling
• Humans
• MicroRNAs/genetics
• Models, Genetic
• Pluripotent Stem Cells/metabolism
• Stem Cells/metabolism

• Myrcludex B
• Species Specificity
• Virology
• Virus Entry

• Gene expression regulation
• Pathway structure
• Risk pathway
• Sample-matched miRNA-mRNA expression profiles

• 3′ UTR
• EOC
• KRAS
• NSCLC
• SNP
• epithelial ovarian cancer
• let-7
• microRNA
• non-small cell lung cancer
• sequence variant

Popular miRNA target prediction techniques use sequence features to determine the functional miRNA target sites. These techniques commonly ignore the cellular conditions in which miRNAs interact with their targets in vivo. Gene expression data are rich resources that can complement sequence features to take into account the context dependency of miRNAs.

We introduce BayMiR, a new computational method, that predicts the functionality of potential miRNA target sites using the activity level of the miRNAs inferred from genome-wide mRNA expression profiles. We also found that mRNA expression variation can be used as another predictor of functional miRNA targets. We benchmarked BayMiR, the expression variation, Cometa, and the TargetScan “context scores” on two tasks: predicting independently validated miRNA targets and predicting the decrease in mRNA abundance in miRNA overexpression assays. BayMiR performed better than all other methods in both benchmarks and, surprisingly, the variation index performed better than Cometa and some individual determinants of the TargetScan context scores. Furthermore, BayMiR predicted miRNA target sets are more consistently annotated with GO and KEGG terms than similar sized random subsets of genes with conserved miRNA seed regions. BayMiR gives higher scores to target sites residing near the poly(A) tail which strongly favors mRNA degradation using poly(A) shortening. Our work also suggests that modeling multiplicative interactions among miRNAs is important to predict endogenous mRNA targets.

We develop a new computational method for predicting the target mRNAs of miRNAs. BayMiR applies a large number of mRNA expression profiles and successfully identifies the mRNA targets and miRNA activities without using miRNA expression data. The BayMiR package is publicly available and can be readily applied to any mRNA expression data sets.

miRNA profiling performed in myogenic cells and biopsies from skeletal muscles has previously identified miRNAs involved in myogenesis.

Here, we have performed miRNA transcriptome profiling in human affinity-purified CD56+ myoblasts induced to differentiate in vitro. In total, we have identified 60 miRNAs differentially expressed during myogenic differentiation. Many were not known for being differentially expressed during myogenic differentiation. Of these, 14 (miR-23b, miR-28, miR-98, miR-103, miR-107, miR-193a, miR-210, miR-324-5p, miR-324-3p, miR-331, miR-374, miR-432, miR-502, and miR-660) were upregulated and 6 (miR-31, miR-451, miR-452, miR-565, miR-594 and miR-659) were downregulated. mRNA transcriptome profiling performed in parallel resulted in identification of 6,616 genes differentially expressed during myogenic differentiation.

This simultaneous miRNA/mRNA transcriptome profiling allowed us to predict with high accuracy target genes of myogenesis-related microRNAs and to deduce their functions.

Non-coding small RNAs, ranging from 20 to 30 nucleotides in length, mediate the regulation of gene expression and play important roles in many biological processes. One class of small RNAs, microRNAs (miRNAs), are highly conserved across taxa and mediate the regulation of the chromatin state and the post-transcriptional regulation of messenger RNA (mRNA). Another class of small RNAs is the Piwi-interacting RNAs, which play important roles in the silencing of transposons and other functional genes. Although the biological functions of the different small RNAs have been elucidated in several laboratory animals, little is known regarding naturally occurring variation in small RNA transcriptomes among closely related species.

We employed next-generation sequencing technology to compare the expression profiles of brain small RNAs between sympatric species of the Japanese threespine stickleback (Gasterosteus aculeatus). We identified several small RNAs that were differentially expressed between sympatric Pacific Ocean and Japan Sea sticklebacks. Potential targets of several small RNAs were identified as repetitive sequences. Female-biased miRNA expression from the old X chromosome was also observed, and it was attributed to the degeneration of the Y chromosome.

Our results suggest that expression patterns of small RNA can differ between incipient species and may be a potential mechanism underlying differential mRNA expression and transposon activity.

• Animals
• Endocrine System Diseases/genetics
• Endocrinology
• Gene Expression Regulation
• Humans
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Models, Biological
• RNA, Messenger/genetics
• RNA, Messenger/metabolism

• Adult
• Azoospermia/genetics
• Biomarkers
• Humans
• Infertility, Male/genetics
• Male
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Oligospermia/genetics
• Semen/metabolism
• Spermatogenesis/genetics

The molecular mechanisms implicated in regionalized gene expression in the human epididymis have not yet been fully elucidated. Interestingly, more than 200 microRNAs (miRNAs) have been identified in the human epididymis and could be involved in the regulation of mRNA stability and post-transcriptional expression in this organ.

Using a miRNA microarray approach, we investigated the correlation between miRNA signatures and gene expression profiles found in three distinct regions (caput, corpus and cauda) of human epididymides from 3 donors. In silico prediction of transcript miRNA targets was performed using TargetScan and Miranda software's. FHCE1 immortalized epididymal cell lines were cotransfected with mimic microRNAs and plasmid constructs containing the 3′UTR of predicted target genes downstream of the luciferase gene.

We identified 35 miRNAs differentially expressed in the distinct segments of the epididymis (fold change ≥2, P-value≤0.01). Among these miRNAs, miR-890, miR-892a, miR-892b, miR-891a, miR-891b belonging to the same epididymis-enriched cluster located on the X chromosome, are significantly more expressed in the corpus and cauda regions than in the caput. Interestingly, a strong negative correlation (r = −0,89, P-value≤0.001) was found between the pattern of expression of miR-892b and its potential mRNA target Esrrg (Estrogen Related Receptor Gamma) and with miR-145 and Cldn10 mRNA (r = −0,92, P-value≤0.001). We confirmed that miR-145 and miR-892b inhibit the expression of the luciferase reporter via Cldn10 and Esrrg 3′ UTRs, respectively.

Our study shows that the expression of miRNAs is segmented along the human epididymis and correlates with the pattern of target gene expression in different regions. Therefore, epididymal miRNAs may be in control of the maintenance of gene expression profile in the epididymis, which dictates segment-specific secretion of proteins and establishes physiological compartments that directly or indirectly affect sperm maturation and fertility.

• Cells, Cultured
• Computational Biology
• Epididymis/metabolism
• Gene Expression Profiling
• Gene Expression Regulation
• Humans
• Male
• MicroRNAs/physiology
• Oligonucleotide Array Sequence Analysis

• #C090473 Canadian Institutes of Health Research

miRNAs are small RNA molecules (′ 22nt) that interact with their corresponding target mRNAs inhibiting the translation of the mRNA into proteins and cleaving the target mRNA. This second effect diminishes the overall expression of the target mRNA. Several miRNA-mRNA relationship databases have been deployed, most of them based on sequence complementarities. However, the number of false positives in these databases is large and they do not overlap completely. Recently, it has been proposed to combine expression measurement from both miRNA and mRNA and sequence based predictions to achieve more accurate relationships. In our work, we use LASSO regression with non-positive constraints to integrate both sources of information. LASSO enforces the sparseness of the solution and the non-positive constraints restrict the search of miRNA targets to those with down-regulation effects on the mRNA expression. We named this method TaLasso (miRNA-Target LASSO).

We used TaLasso on two public datasets that have paired expression levels of human miRNAs and mRNAs. The top ranked interactions recovered by TaLasso are especially enriched (more than using any other algorithm) in experimentally validated targets. The functions of the genes with mRNA transcripts in the top-ranked interactions are meaningful. This is not the case using other algorithms.

TaLasso is available as Matlab or R code. There is also a web-based tool for human miRNAs at http://talasso.cnb.csic.es/.

• Computational Biology/methods
• Humans
• MicroRNAs/metabolism
• Models, Theoretical
• RNA, Messenger/metabolism

• Biomarkers
• Colorectal Neoplasms/genetics
• Colorectal Neoplasms/pathology
• Computational Biology
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• Humans
• MicroRNAs
• Predictive Value of Tests
• Prognosis
• RNA, Messenger/genetics
• Recurrence