Tools4miRs – one place to gather all the tools for miRNA analysis

MiRNAs are short, non-coding molecules that negatively regulate gene expression and thereby play several important roles in living organisms. Dozens of computational methods for miRNA-related research have been developed, which greatly differ in various aspects. The substantial availability of difficult-to-compare approaches makes it challenging for the user to select a proper tool and prompts the need for a solution that will collect and categorize all the methods. Here, we present tools4miRs, the first platform that gathers currently more than 160 methods for broadly defined miRNA analysis. The collected tools are classified into several general and more detailed categories in which the users can additionally filter the available methods according to their specific research needs, capabilities and preferences. Tools4miRs is also a web-based target prediction meta-server that incorporates user-designated target prediction methods into the analysis of user-provided data

MicroRNA-214 targets PTK6 to inhibit tumorigenic potential and increase drug sensitivity of prostate cancer cells.

Prostate cancer is the most commonly diagnosed cancer in men with African American men disproportionally suffering from the burden of this disease. Biomarkers that could discriminate indolent from aggressive and drug resistance disease are lacking. MicroRNAs are small non-coding RNAs that affect numerous physiological and pathological processes, including cancer development and have been suggested as biomarkers and therapeutic targets. In the present study, we investigated the role of miR-214 on prostate cancer cell survival/migration/invasion, cell cycle regulation, and apoptosis. miR-214 was differentially expressed between Caucasian and African American prostate cancer cells. Importantly, miR-214 overexpression in prostate cancer cells induced apoptosis, inhibiting cell proliferation and colony forming ability. miR-214 expression in prostate cancer cells also inhibited cell migration and 3D spheroid invasion. Mechanistically, miR-214 inhibited prostate cancer cell proliferation by targeting protein tyrosine kinase 6 (PTK6). Restoration of PTK6 expression attenuated the inhibitory effect of miR-214 on cell proliferation. Moreover, simultaneous inhibition of PTK6 by ibrutinib and miR-214 significantly reduced cell proliferation/survival. Our data indicates that miR-214 could act as a tumor suppressor in prostate cancer and could potentially be utilized as a biomarker and therapeutic target

Abnormal circulating maternal mirna expression is associated with a low (<4%) cell-free dna fetal fraction

open8noThe present pilot study investigates whether an abnormal miRNA profile in NIPT plasma samples can explain the finding of a low cell-free DNA (cfDNA) fetal fraction (cfDNAff) in euploid fetuses and non-obese women. Twelve women who underwent neoBona® NIPT with a normal fetal karyotype were studied. Six with a cfDNAff &lt; 4% were matched with a control group with normal levels of cfDNAff &gt; 4%. Samples were processed using the nanostring nCounter® platform with a panel of 800 miRNAs. Four of the maternal miRNAs, miR-579, miR-612, miR-3144 and miR-6721, had a significant abnormal expression in patients. A data filtering analysis showed that miR-579, miR-612, miR-3144 and miR-6721 targeted 169, 1, 48 and 136 placenta-specific genes, respectively. miR-579, miR-3144 and miR-6721 shared placenta-specific targeted genes involved in trophoblast invasion and migration pathways (IGF2R, PTCD2, SATB2, PLAC8). Moreover, the miRNA target genes encoded proteins localized in the placenta and involved in the pathogenesis of pre-eclampsia, including chorion-specific transcription factor GCMa, PRG2, Lin-28 Homolog B and IGFBP1. In conclusion, aberrant maternal miRNA expression in circulating plasma could be a source of dysregulating trophoblast invasion and migration and could represent a novel cause of a low cfDNAff in the sera of pregnant women at the time of NIPT analysis.openSantoro G.; Lapucci C.; Giannoccaro M.; Caporilli S.; Rusin M.; Seidenari A.; Ferrari M.; Farina A.Santoro G.; Lapucci C.; Giannoccaro M.; Caporilli S.; Rusin M.; Seidenari A.; Ferrari M.; Farina A

Mapping Posttranscriptional Regulation of the Human Glycome Uncovers microRNA Defining the Glycocode

Cell surface glycans form a critical interface with the biological milieu, informing diverse processes from the inflammatory cascade to cellular migration. Assembly of discrete carbohydrate structures requires the coordinated activity of a repertoire of proteins, including glycosyltransferases and glycosidases. Little is known about the regulatory networks controlling this complex biosynthetic process. Recent work points to a role for microRNA (miRNA) in the regulation of specific glycan biosynthetic enzymes. Herein we take a unique systems-based approach to identify connections between miRNA and the glycome. By using our glycomic analysis platform, lectin microarrays, we identify glycosylation signatures in the NCI-60 cell panel that point to the glycome as a direct output of genomic information flow. Integrating our glycomic dataset with miRNA data, we map miRNA regulators onto genes in glycan biosynthetic pathways (glycogenes) that generate the observed glycan structures. We validate three of these predicted miRNA/glycogene regulatory networks: high mannose, fucose, and terminal β-GalNAc, identifying miRNA regulation that would not have been observed by traditional bioinformatic methods. Overall, our work reveals critical nodes in the global glycosylation network accessible to miRNA regulation, providing a bridge between miRNA-mediated control of cell phenotype and the glycome

LncRNA LINC01857 drives pancreatic adenocarcinoma progression via modulating miR-19a-3p/SMOC2

Objectives: Emerging evidence has demonstrated that LINC01857 exerts a pivotal function in many cancers. However, its function in Pancreatic Ductal Adenocarcinoma (PDAC) still remains unclear. This study was designed to investigate the regulatory character of LINC01857 in PDAC. Methods: Bioinformatic tools and databases were used to seek potential miRNAs and mRNAs. Gene expression was evaluated by Reverse Transcription quantitative real-time Polymerase Chain Reaction (RT-qPCR), and western blot was used for protein level detection. A subcellular fraction assay was done to ascertain the location of LINC01857 in PANC-1 and BxPC-3 human pancreatic cancer cells. CCK-8, EdU, wound healing and Transwell assays were performed to inquire into the influence of LINC01857, and SPARC -related Modular Calcium-binding protein-2 (SMOC2) on cell viability, proliferation, migration, and invasion, respectively. The interaction between LINC01857 and its downstream genes was explored by RNA immunoprecipitation and luciferase reporter assays. Results: LINC01857 levels were significantly elevated in PDAC. Knockdown of LINC01857 significantly restrained the proliferation, migration, invasion, and Epithelial-Mesenchymal Transition (EMT) process of PDAC cells. MiR-19a-3p was a downstream target of LINC01857, and miR-19a-3p levels were significantly decreased in PDAC cells. In addition, SMOC2 expression had a negative correlation with that of miR-19a-3p, and SMOC2 was a downstream target of miR-19a-3p. Furthermore, SMOC2 upregulation partially abolished the inhibitive influence of LINC01857 downregulation on cell proliferation, migration, invasion, and the EMT process. Conclusion: LINC01857 promotes malignant phenotypes of PDAC cells via upregulation of SMOC2 by interacting with miR-19a-3p

MICRO-RNAs E CÂNCER: ABORDAGENS E PERSPECTIVAS / MICRORNAs AND CANCER: APPROACHES AND PERSPECTIVES

Introdução: Diversos estudos foram realizados a fim de compreender a relação entre o micro-RNA e o câncer na última década. Os micro-RNAs possuem aproximadamente 22 nucleotídeos distribuídos em um filamento único que pode regular a expressão de genes em diversos tipos de células, exercendo papéis fundamentais na diferenciação tecidual, ciclo celular, proliferação e apoptose. Objetivo: Esta revisão tem por finalidade compreender o papel dos micro-RNAs no câncer. Alguns estudos vêm destacando a importância dos micro-RNAs, tanto na degradação de RNAs mensageiros, como na repressão da tradução e, constataram que a desregulação destes microRNAs pode estar relacionada à diversas patologias, particularmente o câncer. Situados em regiões com altas probabilidades de mutações, os microRNAs localizados em sítios frágeis estão mais propensos a sofrerem alterações. Estudos descreveram a respeito da expressão diferencial de microRNAs em diversos tipos de câncer, associando genes que codificam microRNAs com as regiões relacionadas ao câncer ou sítios frágeis. A desregulação de sua expressão pode ativar oncogenes e inativar genes supressores de tumor, contribuindo assim para o desenvolvimento do câncer. Desta forma, pode-se afirmar que os micro-RNAs atuam na gênese do câncer. Considerações finais: O avanço da tecnologia da biologia molecular permitiu a utilização dos micro-RNAs como potenciais biomarcadores para o diagnóstico precoce, contribuindo também para o prognóstico e terapêutica do câncer.Palavras-chave: Patologias. Câncer. Oncogene. Expressão gênica.AbstractIntroduction: In the last few years, several studies have been performed for a better understanding of the relationship between microRNA and cancer. MicroRNA has approximately 22 nucleotides distributed in a single filament, which regulate gene expression in many cell types, performing key roles in tissue differentiation, cell cycle, proliferation and apoptosis. Objective: To understand the key roles of microRNAs in cancer. Recently, some studies have reported the importance of microRNAs in messenger RNA degradation and in translation repression. In addition, it was found that microRNA deregulation may be related to many diseases, particularly cancer. Situated in regions with high probability of mutations, microRNAs located at fragile sites are more likely to change. Several studies have found differential expression of microRNAs in many types of cancers, associating genes that encode microRNAs with cancer-related regions or fragile sites. Expression deregulation of microRNAs can activate oncogenes and inactivate tumor suppressor genes, contributing to the development of cancer. Thus, it can be stated that microRNAs play an important role in cancer genesis. Conclusion: Technological advances in the molecular biology allow microRNAs to be potential biomarkers for early diagnosis, also contributing to cancer prognosis and therapy.Keywords: Pathologies. Cancer. Oncogene. Gene expression

A New System for Human MicroRNA functional Evaluation and Network

MicroRNAs are functionally important endogenous non-coding RNAs that silence host genes in animal and plant via destabilizing the mRNAs or preventing the translation. Given the far-reaching implication of microRNA regulation in human health, novel bioinformatics tools are desired to facilitate the mechanistic understanding of microRNA mediated gene regulation, their roles in biological processes, and the functional relevance among microRNAs. However, most state-of-the-art computational methods still focus on the functional study of microRNA targets and there is no e ective strategy to infer the functional similarity among microRNAs. In this study, we developed a new method to quantitatively measure the functional similarity among microRNAs based on the integrated functional annotation data from Gene Ontology, human pathways, and PFam databases. Through analyzing human microRNAs, we further demonstrated the use of the derived microRNA pairwise similarities to discover the cooperative microRNA modules and to construct the genome-scale microRNAmediated gene network in human. The complete results and the similarity assessment system can be freely accessed at (http://sbbi.unl.edu/microRNASim). Adviser: Juan Cu