• miRNA, Analysis, Tools, Bioinformatics, Target gene, Prediction, Tools4miRs

• MicroRNAs/genetics
• Computational Biology/methods
• Software
• Plants/genetics
• RNA, Plant/genetics
• Databases, Genetic

• Animals
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Non-alcoholic Fatty Liver Disease/genetics
• Non-alcoholic Fatty Liver Disease/metabolism
• Non-alcoholic Fatty Liver Disease/pathology
• Mice
• Intra-Abdominal Fat/metabolism
• Disease Models, Animal
• Mice, Inbred C57BL
• Gene Expression Profiling/methods
• Gene Expression Regulation
• Male
• Algorithms

• brain
• endogenous control
• hippocampus
• miRNA
• neural progenitor cell
• neurogenesis
• reference miRNA

• MicroRNAs/genetics
• MicroRNAs/metabolism
• Animals
• Neurogenesis/genetics
• Humans
• Mice
• Hippocampus/metabolism
• Neural Stem Cells/metabolism
• Neural Stem Cells/cytology
• Gene Expression Profiling
• Cell Line
• Mice, Inbred C57BL
• Reference Standards
• Male
• Adult

• R01 MH128022 NIMH NIH HHS
• R21 DA060085 NIDA NIH HHS
• R01 HL126559 NHLBI NIH HHS
• R01 DA050528 NIDA NIH HHS
• DA050528; DA044579; DA059849; HL126559; MH128022; MH072567; DA060085 National Institutes of Health?
• R01 MH072567 NIMH NIH HHS
• R01 DA044579 NIDA NIH HHS
• R01 DA059849 NIDA NIH HHS

• Bioinformatics
• Downstream targets
• Pathway analysis
• RNAseq analysis

• circRNA
• competing endogenous RNA
• gene expression
• hepatocellular carcinoma
• miRNA
• miRNA-circRNA interactions

• Humans
• Carcinoma, Hepatocellular/pathology
• MicroRNAs/genetics
• MicroRNAs/metabolism
• RNA, Circular/genetics
• RNA, Circular/metabolism
• Liver Neoplasms/pathology
• Hepatitis C

The dynamic spectrum of microRNA (miRNA) has grown significantly over the years with its identification and exploration in cancer therapeutics and is currently identified as an important resource for innovative strategies due to its functional behavior for gene regulation and modulation of complex biological networks. The progression of cancer is the consequence of uncontrolled, nonsynchronous procedural faults in the biological system. Diversified and variable cellular response of cancerous cells has always raised challenges in effective cancer therapy. miRNAs, a class of non-coding RNAs (ncRNAs), are the natural genetic gift, responsible to preserve the homeostasis of cell to nurture. The unprecedented significance of endogenous miRNAs has exhibited promising therapeutic potential in cancer therapeutics. Currently, miRNA mimic miR-34, and an antimiR aimed against miR-122 has entered the clinical trials for cancer treatments. This review, highlights the recent breakthroughs, challenges, clinical trials, and advanced delivery vehicles in the administration of miRNA therapies for precision oncology.

• Biomarker
• Cancer
• Data mining
• Extracellular vesicles
• Network
• microRNAs

• cartilage
• circular RNA
• epigenetics
• integrative computational biology
• long non-coding RNA
• microRNA
• network analysis and visualization
• synovium

• Animals
• Arthritis/genetics
• Arthritis/pathology
• Computational Biology
• Epigenesis, Genetic
• Gene Regulatory Networks/genetics
• Humans
• RNA, Long Noncoding/genetics
• Synovial Membrane/pathology

• IK2 CX001269 CSRD VA
• MR/P020941/1 Medical Research Council
• 107471/Z/15/Z Wellcome Trust

• Diagnostic biomarkers
• Liquid biopsy
• Ovarian cancer
• RNA
• Transcriptomics

Small non-coding RNAs have gained substantial attention due to their roles in animal development and human disorders. Among them, microRNAs are special because individual gene sequences are conserved across the animal kingdom. In addition, unique and mechanistically well understood features can clearly distinguish bona fide miRNAs from the myriad other small RNAs generated by cells. However, making this distinction is not a common practice and, thus, not surprisingly, the heterogeneous quality of available miRNA complements has become a major concern in microRNA research. We addressed this by extensively expanding our curated microRNA gene database - MirGeneDB - to 45 organisms, encompassing a wide phylogenetic swath of animal evolution. By consistently annotating and naming 10,899 microRNA genes in these organisms, we show that previous microRNA annotations contained not only many false positives, but surprisingly lacked >2000 bona fide microRNAs. Indeed, curated microRNA complements of closely related organisms are very similar and can be used to reconstruct ancestral miRNA repertoires. MirGeneDB represents a robust platform for microRNA-based research, providing deeper and more significant insights into the biology and evolution of miRNAs as well as biomedical and biomarker research. MirGeneDB is publicly and freely available at http://mirgenedb.org/.

• Cumulus cells
• Insulin resistance
• MAPK signalling pathway
• Polycystic ovary syndrome
• microRNA profile

• Off-target effects
• RNAi drug candidates
• RNAi therapy
• microRNAs
• ncRNAs
• siRNAs

• Amyloid Neuropathies/genetics
• Amyloid Neuropathies/metabolism
• Amyloid Neuropathies/pathology
• Amyloid Neuropathies/therapy
• Animals
• Gene Transfer Techniques
• Humans
• MicroRNAs/antagonists & inhibitors
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Molecular Targeted Therapy/methods
• RNA Interference
• RNA Stability
• RNA, Messenger/antagonists & inhibitors
• RNA, Messenger/genetics
• RNA, Messenger/metabolism
• RNA, Small Interfering/genetics
• RNA, Small Interfering/metabolism
• RNA, Small Interfering/therapeutic use
• RNA, Untranslated/antagonists & inhibitors
• RNA, Untranslated/genetics
• RNA, Untranslated/metabolism
• RNA-Induced Silencing Complex/genetics
• RNA-Induced Silencing Complex/metabolism
• RNAi Therapeutics/methods

• Machine learning
• Plant
• Systematic review
• ab initio
• microRNA

Angiogenesis is a crucial process for organ morphogenesis and growth during development, and it is especially relevant during the repair of wounded tissue in adults. It is coordinated by an equilibrium of pro- and anti-angiogenic factors; nevertheless, when affected, it promotes several diseases. Lately, a growing body of evidence is indicating that non-coding RNAs (ncRNAs), such as miRNAs, circRNAs, and lncRNAs, play critical roles in angiogenesis. These ncRNAs can act in cis or trans and alter gene transcription by several mechanisms including epigenetic processes. In the following pages, we will discuss the functions of ncRNAs in the regulation of angiogenesis and neovascularization, both in normal and disease contexts, from an epigenetic perspective. Additionally, we will describe the contribution of Next-Generation Sequencing (NGS) techniques to the discovery and understanding of the role of ncRNAs in angiogenesis.

• angiogenesis
• circRNA
• epigenetics
• lncRNAs
• miRNAs
• neovascularization
• next generation sequencing
• non-coding RNA

• bibliometric
• bioinformatics tools
• miRNA
• ranking
• text mining

• Algorithms
• Computational Biology/methods
• Machine Learning
• MicroRNAs/chemistry
• MicroRNAs/genetics
• Nucleic Acid Conformation

microRNAs are small non-coding RNA molecules playing a central role in gene regulation. miRBase is the standard reference source for analysis and interpretation of experimental studies. However, the richness and complexity of the annotation is often underappreciated by users. Moreover, even for experienced users, the size of the resource can make it difficult to explore annotation to determine features such as species coverage, the impact of specific characteristics and changes between successive releases. A further consideration is that each new miRBase release contains entries that have had limited review and which may subsequently be removed in a future release to ensure the quality of annotation. To aid the miRBase user, we developed a software tool, miRBaseMiner, for investigating miRBase annotation and generating custom annotation sets. We apply the tool to characterize each release from v9.2 to v22 to examine how annotation has changed across releases and highlight some of the annotation features that users should keep in mind when using for miRBase for data analysis. These include: (1) entries with identical or very similar sequences; (2) entries with multiple annotated genome locations; (3) hairpin precursor entries with extremely low-estimated minimum free energy; (4) entries possessing reverse complementary; (5) entries with 3ʹ poly(A) ends. As each of these factors can impact the identification of dysregulated features and subsequent clinical or biological conclusions, miRBaseMiner is a valuable resource for any user using miRBase as a reference source.

• Microrna
• NGS
• annotation
• characterization
• miRBase
• miRBaseMiner
• miRNA

• Bovine tuberculosis
• computational
• microRNA
• pathway prediction
• target gene

• Algorithm
• Analysis tools
• Database
• Machine learning tools
• Transcription factor
• microRNA

• Analysis
• Bioinformatics
• Prediction
• Target gene
• Tools
• miRNA

• Animals
• MicroRNAs/genetics
• Plants/genetics
• RNA, Plant/genetics
• Software

• cutaneous melanoma
• microRNA
• non-coding RNA

• Apoptosis/genetics
• Biomarkers, Tumor/genetics
• Cell Cycle/genetics
• Cell Proliferation/genetics
• Gene Expression Regulation, Neoplastic
• Humans
• Melanoma/diagnosis
• Melanoma/genetics
• Melanoma/immunology
• MicroRNAs/metabolism
• MicroRNAs/physiology
• Prognosis
• RNA, Long Noncoding/metabolism
• RNA, Long Noncoding/physiology
• Skin Neoplasms/diagnosis
• Skin Neoplasms/genetics
• Skin Neoplasms/immunology
• Tumor Escape/genetics
• Melanoma, Cutaneous Malignant

• IG 18464 Associazione Italiana per la Ricerca sul Cancro
• Fondazione Pallotti (University of Bologna)

• Annotation
• Bioinformatics
• miRBase repository
• miRNA
• miRNA family
• miRNA information retrieval

• Algorithms
• Animals
• Computational Biology/methods
• Databases, Nucleic Acid
• Gene Ontology
• Humans
• MicroRNAs/classification
• MicroRNAs/genetics
• Molecular Sequence Annotation
• Software
• Terminology as Topic

• HPV
• HPV integration sites
• bioinformatics tools
• cervical cancer
• human genome variants
• miRNAs
• microRNAs
• secondary structure

Ovarian cancer is the leading cause of death by gynecologic cancers in the Western world. The aim of the study was to identify microRNAs (miRNAs) associated with prognosis and/or resistance to chemotherapy among patients with epithelial ovarian cancer.

Using information from the Pelvic Mass Study we identified a cohort of women with epithelial ovarian cancer. Tumor tissues were then collected and analyzed by global miRNA microarrays. MiRNA profiling was then linked to survival and time to progression using Cox proportional-hazards regression models. Logistic regression models were used for the analysis of resistance to chemotherapy. Our results were validated using external datasets retrieved from the NCBI Gene Expression Omnibus database.

A total of 197 patients with epithelial ovarian cancer were included for miRNA microarray analysis. In multivariate analyses we identified a number of miRNAs significantly correlated with overall survival (miR-1183 (HR: 1.42, 95% CI:1.17–1.74, p = 0.0005), miR-126-3p (HR: 1.38, 95% CI:1.11–1.71, p = 0.0036), time to progression (miR-139-3p (HR: 1.48, 95% CI: 1.13–1.94, p = 0.0047), miR-802 (HR: 0.48, 95% CI: 0.29–0.78, p = 0.0035)), progression free survival (miR-23a-5p (HR:1.32, 95% CI:1.09–1.61, p = 0.004), miR-23a-3p (HR:1.70, 95% CI:1.15–2.51, p = 0.0074), miR-802 (HR: 0.48, 95% CI: 0.29–0.80, p = 0.0048)), and resistance to chemotherapy (miR-1234 (HR: 0.26, 95% CI: 0.11–0.64, p = 0.003)). A few miRNAs identified in our training cohort, were validated in external cohorts with similar results.

Eight miRNAs were identified as significant predictors of overall survival, progression free survival, time to progression, and chemotherapy resistance. A number of these miRNAs were significantly validated using external datasets. Inter-platform and inter-laboratory variations may have influence on the ability to compare and reproduce miRNA results. The use of miRNAs as potential markers of relapse and survival in ovarian cancer warrants further investigation.

• Adult
• Aged
• Aged, 80 and over
• Carcinoma, Ovarian Epithelial/genetics
• Carcinoma, Ovarian Epithelial/metabolism
• Carcinoma, Ovarian Epithelial/mortality
• Carcinoma, Ovarian Epithelial/pathology
• Databases, Nucleic Acid
• Disease-Free Survival
• Female
• Gene Expression Profiling
• Humans
• MicroRNAs/biosynthesis
• MicroRNAs/genetics
• Middle Aged
• Oligonucleotide Array Sequence Analysis
• Ovarian Neoplasms/genetics
• Ovarian Neoplasms/metabolism
• Ovarian Neoplasms/mortality
• Ovarian Neoplasms/pathology
• RNA, Neoplasm/biosynthesis
• RNA, Neoplasm/genetics
• Survival Rate

• FOXO1
• Hsa-miR-27a
• Integrated meta-analysis
• Ovarian cancer
• Prognosis

Despite the established contribution of deregulated microRNA (miRNA) function to carcinogenesis, relatively few miRNA-cancer gene interactions have been validated, making it difficult to appreciate the true complexity of miRNA-cancer gene regulatory networks.

In this effort, we identify miRNA interactomes of 17 well-established cancer genes, involved in various cancer types, through a miRNome-wide 3’ UTR reporter screening. Using a novel and performant strategy for high-throughput screening data analysis, we identify 390 interactions, quadrupling the size of the known miRNA interactome for the cancer genes under investigation. Clear enrichments of established and predicted interactions underscore the validity of the interactome data set. Interactomes appear to be primarily driven by canonical binding site interactions. Nonetheless, non-canonical binding sites, such as offset 6mer and seed-mismatched or G:U wobble sites, also have regulatory activity, albeit clearly less pronounced. Furthermore, we observe enhanced regulation in the presence of 3’ supplementary pairing for both canonical and non-canonical binding sites.

Altogether, the cancer gene-miRNA interactome data set represents a unique resource that will aid in the unraveling of regulatory miRNA networks and the dynamic regulation of key protein-coding cancer genes. In addition, it uncovers aspects of the functional miRNA binding site’s architecture and the relative contributions of different binding site types.

• 3' Untranslated Regions/genetics
• Area Under Curve
• Binding Sites
• Datasets as Topic
• Gene Regulatory Networks
• Genes, Reporter
• High-Throughput Screening Assays/methods
• Humans
• MicroRNAs/genetics
• Molecular Sequence Annotation
• Mutagenesis, Site-Directed
• Oncogenes
• ROC Curve
• Reproducibility of Results
• Transfection

• Stichting Tegen Kanker (BE)
• Vlaamse Liga Tegen Kanker (BE)
• Universiteit Gent (BE)
• Fonds voor Wetenschappelijk Onderzoek Vlaanderen (BE)
• Fournier-Majoie Foundation (BE)
• Cancer Plan from the Federal Public Service of Health (BE)
• Children Cancer Fund Ghent (BE)
• Belgian Program of Interuniversity Poles of Attraction (BE)
• ASSET FP7 Consortium

Asbestos is a harmful and exceptionally persistent natural material. Malignant mesothelioma (MM), an asbestos-related disease, is an insidious, lethal cancer that is poorly responsive to current treatments. Minimally invasive, specific, and sensitive biomarkers providing early and effective diagnosis in high-risk patients are urgently needed. MicroRNAs (miRNAs, miRs) are endogenous, non-coding, small RNAs with established diagnostic value in cancer and pollution exposure. A systematic review and a qualitative meta-analysis were conducted to identify high-confidence miRNAs that can serve as biomarkers of asbestos exposure and MM.

The major biomedical databases were systematically searched for miRNA expression signatures related to asbestos exposure and MM. The qualitative meta-analysis applied a novel vote-counting method that takes into account multiple parameters. The most significant miRNAs thus identified were then subjected to functional and bioinformatic analysis to assess their biomarker potential.

A pool of deregulated circulating and tissue miRNAs with biomarker potential for MM was identified and designated as “mesomiRs” (MM-associated miRNAs). Comparison of data from asbestos-exposed and MM subjects found that the most promising candidates for a multimarker signature were circulating miR-126-3p, miR-103a-3p, and miR-625-3p in combination with mesothelin. The most consistently described tissue miRNAs, miR-16-5p, miR-126-3p, miR-143-3p, miR-145-5p, miR-192-5p, miR-193a-3p, miR-200b-3p, miR-203a-3p, and miR-652-3p, were also found to provide a diagnostic signature and should be further investigated as possible therapeutic targets.

The qualitative meta-analysis and functional investigation confirmed the early diagnostic value of two miRNA signatures for MM. Large-scale, standardized validation studies are needed to assess their clinical relevance, so as to move from the workbench to the clinic.

• asbestos
• biomarker
• mesothelioma
• microRNA
• systematic review

Long-term alcohol use can result in lasting changes in brain function, ultimately leading to alcohol dependence. These functional alterations arise from dysregulation of complex gene networks, and growing evidence implicates microRNAs as key regulators of these networks. We examined time- and brain region-dependent changes in microRNA expression after chronic intermittent ethanol (CIE) exposure in C57BL/6J mice. Animals were sacrificed at 0, 8, and 120h following the last exposure to four weekly cycles of CIE vapor and we measured microRNA expression in prefrontal cortex (PFC), nucleus accumbens (NAC), and amygdala (AMY). The number of detected (395–419) and differentially expressed (DE, 42–47) microRNAs was similar within each brain region. However, the DE microRNAs were distinct among brain regions and across time within each brain region. DE microRNAs were linked with their DE mRNA targets across each brain region. In all brain regions, the greatest number of DE mRNA targets occurred at the 0 or 8h time points and these changes were associated with microRNAs DE at 0 or 8h. Two separate approaches (discrete temporal association and hierarchical clustering) were combined with pathway analysis to further characterize the temporal relationships between DE microRNAs and their 120h DE targets. We focused on targets dysregulated at 120h as this time point represents a state of protracted withdrawal known to promote an increase in subsequent ethanol consumption. Discrete temporal association analysis identified networks with highly connected genes including ERK1/2 (mouse equivalent Mapk3, Mapk1), Bcl2 (in AMY networks) and Srf (in PFC networks). Similarly, the cluster-based analysis identified hub genes that include Bcl2 (in AMY networks) and Srf in PFC networks, demonstrating robust microRNA-mRNA network alterations in response to CIE exposure. In contrast, datasets utilizing targets from 0 and 8h microRNAs identified NF-kB-centered networks (in NAC and PFC), and Smad3-centered networks (in AMY). These results demonstrate that CIE exposure results in dynamic and complex temporal changes in microRNA-mRNA gene network structure.

MicroRNAs (miRNAs) encoded by viral genome or host have been found participating in host-microbe interactions. Differential expression profiles of miRNAs were shown linking to specific disease pathologies which indicated its potency as diagnostic/prognostic biomarkers of infectious disease. This was emphasized by the discovery of circulating miRNAs which were found to be remarkably stable in mammalian biofluids. Standardized methods of miRNA quantification including RNA isolation should be established before they will be ready for use in clinical practice.

Papillary Thyroid Carcinoma (PTC) is the most frequent thyroid cancer. Although several PTC-specific miRNA profiles have been reported, only few upregulated miRNAs are broadly recognized, while less consistent data are available about downregulated miRNAs. In this study we investigated miRNA deregulation in PTC by miRNA microarray, analysis of a public dataset from The Cancer Genome Atlas (TCGA), literature review and meta-analysis based on a univocal miRNA identifier derived from miRBase v21. A list of 18 miRNAs differentially expressed between PTC and normal thyroid was identified and validated in the TCGA dataset. Furthermore, we compared our signature with miRNA profiles derived from 15 studies selected from literature. Then, to select possibly functionally relevant miRNA, we integrated our miRNA signature with those from two in vitro cell models based on the PTC-driving oncogene RET/PTC1. Through this strategy, we identified commonly deregulated miRNAs, including miR-451a, which emerged also by our meta-analysis as the most frequently reported downregulated miRNA. We showed that lower expression of miR-451a correlates with aggressive clinical-pathological features of PTC as tall cell variant, advanced stage and extrathyroid extension. In addition, we demonstrated that ectopic expression of miR-451a impairs proliferation and migration of two PTC-derived cell lines, reduces the protein levels of its recognized targets MIF, c-MYC and AKT1 and attenuates AKT/mTOR pathway activation.

Overall, our study provide both an updated overview of miRNA deregulation in PTC and the first functional evidence that miR-451a exerts tumor suppressor functions in this neoplasia.

• AKT pathway
• RET/PTC
• miR-451a
• miRNA
• papillary thyroid carcinoma

• SNPs
• miRNA
• microRNA
• pre-miRNA

Chronic obstructive pulmonary disease (COPD) is characterized by a progressive airflow limitation and is associated with a chronic inflammatory response in both airways and lungs. microRNAs (miRNAs) are often highly conserved between species and have an intricate role within homeostatic conditions and immune responses. Also, miRNAs are dysregulated in smoking-associated diseases. We investigated the miRNA profile of 523 miRNAs by stem-loop RT-qPCR in lung tissue and cell-free bronchoalveolar lavage (BAL) supernatant of mice exposed to air or cigarette smoke (CS) for 4 or 24 weeks. After 24 weeks of CS exposure, 31 miRNAs were differentially expressed in lung tissue and 78 in BAL supernatant. Next, we correlated the miRNA profiling data to inflammation in BAL and lung, obtained by flow cytometry or ELISA. In addition, we surveyed for overlap with newly assessed miRNA profiles in bronchial biopsies and with previously assessed miRNA profiles in lung tissue and induced sputum supernatant of smokers with COPD. Several miRNAs showed concordant differential expression between both species including miR-31*, miR-155, miR-218 and let-7c. Thus, investigating miRNA profiling data in different compartments and both species provided accumulating insights in miRNAs that may be relevant in CS-induced inflammation and the pathogenesis of COPD.

With persistent inconsistencies in colorectal cancer (CRC) miRNAs expression data, it is crucial to shift toward inclusion of a “pre-laboratory” integrated analysis to expedite effective precision medicine and translational research. Aberrant expression of hsa-miRNA-195 (miR-195) which is distinguished as a clinically noteworthy miRNA has previously been observed in multiple cancers, yet its role in CRC remains unclear.

In this study, we performed an integrated analysis of seven CRC miRNAs expression datasets. The expression of miR-195 was validated in The Cancer Genome Atlas (TCGA) datasets, and an independent validation sample cohort. Colon cancer cells were transfected with miR-195 mimic and inhibitor, after which cell proliferation, colony formation, migration, invasion, and dual luciferase reporter were assayed. Xenograft mouse models were used to determine the role of miR-195 in CRC tumorigenicity in vivo.

Four downregulated miRNAs (hsa-let-7a, hsa-miR-125b, hsa-miR-145, and hsa-miR-195) were demonstrated to be potentially useful diagnostic markers in the clinical setting. CRC patients with a decreased level of miR-195-5p in tumor tissues had significantly shortened survival as revealed by the TCGA colon adenocarcinoma (COAD) dataset and our CRC cohort. Overexpression of miR-195-5p in DLD1 and HCT116 cells repressed cell growth, colony formation, invasion, and migration. Inhibition of miR-195-5p function contributed to aberrant cell proliferation, migration, invasion, and epithelial mesenchymal transition (EMT). We identified miR-195-5p binding sites within the 3’-untranslated region (3′-UTR) of the human yes-associated protein (YAP) mRNA. YAP1 expression was downregulated after miR-195-5p treatment by qRT-PCR analysis and western blot.

Four downregulated miRNAs were shown to be prime candidates for a panel of biomarkers with sufficient diagnostic accuracy for CRC in a clinical setting. Our integrated microRNA profiling approach identified miR-195-5p independently associated with prognosis in CRC. Our results demonstrated that miR-195-5p was a potent suppressor of YAP1, and miR-195-5p-mediated downregulation of YAP1 significantly reduced tumor development in a mouse CRC xenograft model. In the clinic, miR-195-5p can serve as a prognostic marker to predict the outcome of the CRC patients.

The online version of this article (doi:10.1186/s13045-017-0445-8) contains supplementary material, which is available to authorized users.

• Biomarker
• Colorectal cancer (CRC)
• Epithelial mesenchymal transition (EMT)
• Hsa-miRNA-195(miR-195)
• Prognosis
• YAP1

In the last decade, the role for noncoding RNAs in disease was clearly established, starting with microRNAs and later expanded towards long noncoding RNAs. This was also the case for T cell acute lymphoblastic leukemia, which is a malignant blood disorder arising from oncogenic events during normal T cell development in the thymus. By studying the transcriptomic profile of protein-coding genes, several oncogenic events leading to T cell acute lymphoblastic leukemia (T-ALL) could be identified. In recent years, it became apparent that several of these oncogenes function via microRNAs and long noncoding RNAs. In this review, we give a detailed overview of the studies that describe the noncoding RNAome in T-ALL oncogenesis and normal T cell development.

• LncRNA
• MicroRNA
• T-ALL
• Thymocytes

The medial entorhinal cortex (MEC) is important in spatial navigation and memory formation and its layers have distinct neuronal subtypes, connectivity, spatial properties, and disease susceptibility. As little is known about the molecular basis for the development of these laminar differences, we analyzed microRNA (miRNA) and messenger RNA (mRNA) expression differences between rat MEC layer II and layers III–VI during postnatal development. We identified layer and age-specific regulation of gene expression by miRNAs, which included processes related to neuron specialization and locomotor behavior. Further analyses by retrograde labeling and expression profiling of layer II stellate neurons and in situ hybridization revealed that the miRNA most up-regulated in layer II, miR-143, was enriched in stellate neurons, whereas the miRNA most up-regulated in deep layers, miR-219-5p, was expressed in ependymal cells, oligodendrocytes and glia. Bioinformatics analyses of predicted mRNA targets with negatively correlated expression patterns to miR-143 found that miR-143 likely regulates the Lmo4 gene, which is known to influence hippocampal-based spatial learning.

• Brain development
• Medial entorhinal cortex
• MiRNA
• Stellate neurons

Innate and acquired chemoresistance exhibited by most tumours exposed to conventional chemotherapeutic agents account for the majority of relapse cases in cancer patients. Such chemoresistance phenotypes are of a multi-factorial nature from multiple key molecular players. The discovery of the RNA interference pathway in 1998 and the widespread gene regulatory influences exerted by microRNAs (miRNAs) and other non-coding RNAs have certainly expanded the level of intricacy present for the development of any single physiological phenotype, including cancer chemoresistance. This review article focuses on the latest research efforts in identifying and validating specific key molecular players from the two main families of non-coding RNAs, namely miRNAs and long non-coding RNAs (lncRNAs), having direct or indirect influences in the development of cancer drug resistance properties and how such knowledge can be utilised for novel theranostics in oncology.

• cancer
• chemoresistance
• drug resistance
• lncRNA
• miRNA
• microRNA
• tumour

• adipocytes
• metabolism
• microRNA
• non-alcoholic hepato-steatosis
• type 2 diabetes mellitus
• β-cells

• Animals
• Homeostasis/physiology
• Humans
• Metabolism/genetics
• MicroRNAs/physiology

• Normalization
• RT-qPCR
• Small RNA sequencing
• miRNA
• miRNA annotation

• Gene Expression Profiling/methods
• Humans
• MicroRNAs/genetics
• RNA, Small Untranslated/genetics
• Real-Time Polymerase Chain Reaction/methods
• Sequence Analysis, RNA/methods

• T-ALL
• T-cell acute lymphoblastic leukemia
• TAL1
• microRNAs
• post-transcriptional regulation

A large number of studies have focused on identifying molecular biomarkers, including microRNAs (miRNAs) to aid in the diagnosis and prognosis of the most common subtypes of non-Hodgkin lymphoma (NHL), Diffuse Large B-cell Lymphoma and Follicular Lymphoma. NHL is difficult to diagnose and treat with many cases becoming resistant to chemotherapy, hence the need to identify improved biomarkers to aid in both diagnosis and treatment modalities. This review summarises more recent research on the dysregulated miRNA expression profiles found in NHL, as well as the regulatory role and biomarker potential of cellular and circulating miRNAs found in tissue and serum, respectively. In addition, the emerging field of research focusing on miRNA single nucleotide polymorphisms (miRSNPs) in genes of the miRNA biogenesis pathway, in miRNA genes themselves, and in their target sites may provide new insights on gene expression changes in these genes. These miRSNPs may impact miRNA networks and have been shown to play a role in a host of different cancer types including haematological malignancies. With respect to NHL, a number of SNPs in miRNA-binding sites in target genes have been shown to be associated with overall survival.

• B-cell lymphoma
• biomarker
• circulating miRNA
• haematological malignancies
• lymphoid neoplasia
• miRSNP (micro-RNA single nucleotide polymorphism)
• micro-RNA (miRNA/miR)

MicroRNAs (miRNAs) are often deregulated in cancer and are thought to play an important role in cancer development. Large amount of differentially expressed miRNAs have been identified in various cancers by using high-throughput methods. It is therefore quite important to make a comprehensive collection of these miRNAs and to decipher their roles in oncogenesis and tumor progression. In 2010, we presented the first release of dbDEMC, representing a database for collection of differentially expressed miRNAs in human cancers obtained from microarray data. Here we describe an update of the database. dbDEMC 2.0 documents 209 expression profiling data sets across 36 cancer types and 73 subtypes, and a total of 2224 differentially expressed miRNAs were identified. An easy-to-use web interface was constructed that allows users to make a quick search of the differentially expressed miRNAs in certain cancer types. In addition, a new function of ‘meta-profiling’ was added to view differential expression events according to user-defined miRNAs and cancer types. We expect this database to continue to serve as a valuable source for cancer investigation and potential clinical application related to miRNAs. dbDEMC 2.0 is freely available at http://www.picb.ac.cn/dbDEMC.

Our goal was to design a customized microarray, arrEYE, for high-resolution copy number variant (CNV) analysis of known and candidate genes for inherited retinal dystrophy (iRD) and retina-expressed noncoding RNAs (ncRNAs).

arrEYE contains probes for the full genomic region of 106 known iRD genes, including those implicated in retinitis pigmentosa (RP) (the most frequent iRD), cone–rod dystrophies, macular dystrophies, and an additional 60 candidate iRD genes and 196 ncRNAs. Eight CNVs in iRD genes identified by other techniques were used as positive controls. The test cohort consisted of 57 patients with autosomal dominant, X-linked, or simplex RP.

In an RP patient, a novel heterozygous deletion of exons 7 and 8 of the HGSNAT gene was identified: c.634-408_820+338delinsAGAATATG, p.(Glu212Glyfs*2). A known variant was found on the second allele: c.1843G>A, p.(Ala615Thr). Furthermore, we expanded the allelic spectrum of USH2A and RCBTB1 with novel CNVs.

The arrEYE platform revealed subtle single-exon to larger CNVs in iRD genes that could be characterized at the nucleotide level, facilitated by the high resolution of the platform. We report the first CNV in HGSNAT that, combined with another mutation, leads to RP, further supporting its recently identified role in nonsyndromic iRD.

Genet Med19 4, 457–466.