Institute of Human Genetics, Saarland University, Building 60, 66421, Homburg, Germany.
Published: July 2019
AI Article Synopsis
Article Abstract
Background: Micro(mi)RNAs are increasingly recognized as central regulators of immune cell function. While it has been predicted that miRNAs have multiple targets, the majority of these predictions still await experimental confirmation. Here, miR-34a, a well-known tumor suppressor, is analyzed for targeting genes involved in immune system processes of leucocytes.
Methods: Using an in-silico approach, we combined miRNA target prediction with GeneTrail2, a web tool for Multi-omics enrichment analysis, to identify miR-34a target genes, which are involved in the immune system process subcategory of Gene Ontology.
Results: Out of the 193 predicted target genes in this subcategory we experimentally tested 22 target genes and confirmed binding of miR-34a to 14 target genes including VAMP2, IKBKE, MYH9, MARCH8, KLRK1, CD11A, TRAFD1, CCR1, PYDC1, PRF1, PIK3R2, PIK3CD, AP1B1, and ADAM10 by dual luciferase assays. By transfecting Jurkat, primary CD4 and CD8 T cells with miR-34a, we demonstrated that ectopic expression of miR-34a leads to reduced levels of endogenous VAMP2 and CD11A, which are central to the analyzed subcategories. Functional downstream analysis of miR-34a over-expression in activated CD8 T cells exhibits a distinct decrease of PRF1 secretion.
Conclusions: By simultaneous targeting of 14 mRNAs miR-34a acts as major hub of T cell regulatory networks suggesting to utilize miR-34a as target of intervention towards a modulation of the immune responsiveness of T-cells in a broad tumor context.
Background: Abnormal expression of six-transmembrane epithelial antigen of prostate 4 (STEAP4) has been implicated in the carcinogenesis of hepatocellular carcinoma (HCC). However, the biological role and regulatory mechanisms of STEAP4 in HCC remain unclear.
Methods And Results: Here, we analyzed STEAP4 expression levels and differentially expressed genes (DEGs) between STEAP4 high- and low-expression groups using multiple databases.
Global Health and Tropical Medicine- Institute of Hygiene and Tropical Medicine, NOVA University of Lisbon, Rua da Junqueira 100, 1349-008, Lisbon, Portugal.
Background: Tick-borne rickettsioses (TBR) are emerging, neglected, zoonoses, caused by intracellular α-proteobacteria of the genus Rickettsia, that pose a growing public health concern. The aim of the present study was to evaluate rickettsial infections in questing ticks collected from four different ecological areas in mainland Portugal.
Methods: Over a two-year period, a total of 707 questing ticks were collected.
Background: Diabetic retinopathy (DR) is the most important complication of Type 2 Diabetes (T2D) in eyes. Despite its prevalence, the early detection and management of DR continue to pose considerable challenges. Our research aims to elucidate potent drug targets that could facilitate the identification of DR and propel advancements in its therapeutic strategies.
Background: Periodontitis is among the most prevalent inflammatory conditions and greatly impacts oral health. This study aimed to elucidate the role of basement membrane-related genes in the pathogenesis and diagnosis of periodontitis.
Methods: GSE10334 was used for identification of hub genes via the differential analysis, protein-protein interaction network, MCC and DMNC algorithms, and evaluation via LASSO regression and support vector machine analysis to identify basement membrane-related markers in patients with periodontitis.
Comorbidity among atopic diseases (ADs) and gastrointestinal diseases (GIDs) has been repeatedly demonstrated by epidemiological studies, whereas the shared genetic liability remains largely unknown. Here we establish an atlas of the shared genetic architecture between 10 ADs or related traits and 11 GIDs, comprehensively investigating the comorbidity-associated genomic regions, cell types, genes and genetically predicted causality. Although distinct genetic correlations between AD-GID are observed, including 14 genome-wide and 28 regional correlations, genetic factors of Crohn's disease (CD), ulcerative colitis (UC), celiac disease and asthma subtypes are converged on CD4 T cells consistently across relevant tissues.
