Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA174164 | ENA |
REPOSITORIES: ENA
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Project description:MicroRNAs (miRNAs) post-transcriptionally regulate gene expression by inhibiting protein synthesis of target messenger RNAs (mRNAs). MicroRNA-142 (miR-142), which has tumor-suppressive properties, was functionally deleted by CRISPR/Cas9 knockout in cell lines derived from diffuse large B-cell lymphoma (DLBCL), a highly aggressive tumor that represents about 30% of non-Hodgkin lymphoma worldwide. Mutations in miR-142 affect about 20% of all cases of DLBCL. By proteome analyses, the miR-142 knockout resulted in a consistent up-regulation of 52 but also down-regulation of 41 proteins in the GC-DLBCL lines BJAB and SUDHL4. Various mitochondrial ribosomal proteins were up-regulated in line with their pro-tumorigenic properties, while proteins necessary for MHC-I presentation were down-regulated in accordance with the finding that miR-142 knockout mice have a defective immune response. Of the deregulated proteins/genes, CFL2, CLIC4, STAU1, and TWF1 are known targets of miR-142, and we could additionally confirm AKT1S1, CCNB1, LIMA1, and TFRC as new targets of miR-142-3p or -5p. We further show that seed-sequence mutations of miR-142 can be used to confirm potential targets and that miRNA knockout cell lines might thus be used to identify novel targets of miRNAs. Due to the complex contribution of miRNAs within cellular regulatory networks, in particular when a miRNA highly present in the RISC complex is deleted and can be replaced by other endogenous miRNAs, primary effects on gene expression may be covered by secondary layers of regulation
2023-03-10 | PXD037148 | Pride
Project description:Deregulation of the translational machinery is emerging as a critical contributor to lymphomagenesis. Various miRNA alterations have been identified in lymphoma, but their role in disrupting the cap-dependent translation regulation complex remains poorly understood. Here, we demonstrate the translation initiation factor, eIF4GII, as a direct target and major mediator of miR-520c-3p function through 3’UTR of eIF4GII mRNA. We established that elevated miR-520c-3p represses translation, initiates premature senescence and blocks cell proliferation in diffuse large B-cell lymphoma (DLBCL). Moreover, miR-520c-3p overexpression diminishes DLBCL cells colony formation and reduces tumor growth in a lymphoma xenograft mouse model. miR-520c-3p overexpressing cells display lowered eIF4GII levels. Consequently, downregulation of eIF4GII by siRNA induces cellular senescence, decreases cell proliferation and ability to form colonies. Our in vitro and in vivo findings we further validated in patient samples; DLBCL primary cells demonstrated low miR-520c-3p levels with reciprocally highly up-regulated eIF4GII protein expression. In contrast, normal donor B-cell lymphocytes had low levels of eIF4GII protein and elevated miR-520c-3p levels. Our results provide evidence that the tumor suppressor effect of miR-520c-3p is mediated through repression of cap-dependent translation while inducing senescence and that eIF4GII is a key effector of this anti-tumor activity. These findings may have implications for therapeutic interventions in patients with DLBCL.
2014-03-19 | GSE40489 | GEO
Project description:Primary testicular (PT) diffuse large B-cell lymphoma (DLBCL) is a rare and aggressive lymphoma with distinct clinical and molecular characteristics. To further improve the prognosis of PT-DLBCL, not only the common features of PT-DLBCL, but also the molecular heterogeneity within the PT-DLBCL entity, need to be better understood. In this study, 2083 microRNAs and 13 housekeeping genes in RNA samples from 150 patients with PT-DLBCL were sequenced using next-generation sequencing technology. After quality-control, CPM standardization, and normalization, microRNA profiling data were obtained for 113 patients with PT-DLBCL. Our analysis identified a microRNA signature (comprising 35 microRNAs) that clustered 113 patients with PT-DLBCL into two distinct clusters. Patients with high expression of 16 microRNAs (miR-514a-3p, miR-202-3p, miR-509-5p, miR-509-3-5p, miR-506-3p, miR-508-3p, miR-514b-5p, miR-513a-5p, miR-510-5p, miR-513b-5p, miR-513c-5p, miR-508-5p, miR-509-3p, miR-202-5p, miR-507, and miR-514b-3p) had significantly better survival.
2025-07-23 | GSE298277 | GEO
Project description:Mature B-cell differentiation provides an important mechanism for the acquisition of adaptive immunity. Malignancies derived from mature B-cells constitute the majority of leukemias and lymphomas. These malignancies often maintain the characteristics of the normal B-cells that they are derived from, a feature that is frequently used in their diagnosis. The role of microRNAs in mature B-cells is largely unknown. Through concomitant microRNA and mRNA-profiling, we demonstrate a potential regulatory role for microRNAs at every stage of the mature B-cell differentiation process. Further, we have experimentally identified a direct role for the microRNA-regulation of key transcription factors in B-cell differentiation: LMO2 and PRDM1 (Blimp1). We also profiled microRNA of B-cell tumors derived from diffuse large B cell lymphoma, Burkitt lymphoma and chronic lymphocytic leukemia. We found that in contrast to many other malignancies, common B-cell malignancies do not down-regulate microRNAs, but rather maintain the microRNA-expression patterns of their normal B-cell counterparts. Further, each tumor-type maintained the expression of the lineage-specific microRNAs and expression of these lineage-specific microRNAs could correctly predict the lineage of B-cell malignancies in over 90% of the cases. Thus, our data demonstrate that microRNAs may be important in maintaining the mature B-cell phenotype in normal and malignant B-cells. Burkitt lymphoma, Chronic Lymphocytic Leukemia (Mutated), Chronic Lymphocytic Leukemia (Unmutated), Activated B cell-like Diffuse large B cell lymphoma, and Germinal Center-like Diffuse large B cell lymphoma Samples,
2009-03-16 | E-GEOD-15250 | biostudies-arrayexpress
Project description:High-throughput sequencing of primary cutaneous follicle center lymphoma (PCFCL), primary cutaneous diffuse large B-cell lymphoma, leg type (PCLBCL-LT) and in vitro activated peripheral blood B-cells. We performed high-throughput sequencing analysis on frozen tumor biopsies from 19 cases of PCFCL and PCLBCL-LT to establish microRNA profiles. Cluster analysis of the complete microRNome could not distinguish between the two subtypes, but 16 single microRNAs were found to be differentially expressed. Lymphoma miRNA profiles of were generated by deep sequencing, using Illumina Genome Analyzer II.
2013-10-18 | E-GEOD-51359 | biostudies-arrayexpress
Project description:High-throughput sequencing of primary cutaneous follicle center lymphoma (PCFCL), primary cutaneous diffuse large B-cell lymphoma, leg type (PCLBCL-LT) and in vitro activated peripheral blood B-cells. We performed high-throughput sequencing analysis on frozen tumor biopsies from 19 cases of PCFCL and PCLBCL-LT to establish microRNA profiles. Cluster analysis of the complete microRNome could not distinguish between the two subtypes, but 16 single microRNAs were found to be differentially expressed.
2013-10-18 | GSE51359 | GEO
Project description:Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide, with limited effective treatment options. Recent studies highlight the emerging role of microRNAs in HCC biology, including microRNA-372-3p (miR-372-3p), but its precise function in HCC remains controversial. Here, we investigated the role of miR-372-3p in HCC using a transcriptomic approach. Overexpression of miR-372-3p in HCC cell lines significantly impaired proliferation, migration, invasion, and colony formation, indicating a tumor-suppressive function. RNA sequencing and Gene Set Enrichment Analysis (GSEA) revealed downregulation of genes involved in fatty acid metabolism, specifically fatty acid oxidation (FAO). Consistently, miR-372-3p overexpression increased lipid droplet accumulation and triglyceride levels while inhibiting FAO, leading to impaired lipid utilization under glucose deprivation and compromised interactions of lipid droplets with mitochondria and lysosomes. Mechanistically, we identified CPT1A and ACSL4 as direct targets of miR-372-3p using bioinformatics and dual luciferase assays. These findings demonstrate that miR-372-3p acts as a tumor suppressor in HCC by inhibiting FAO and disrupting lipid metabolism, suggesting a potential therapeutic target for HCC treatment.
2025-09-11 | GSE290065 | GEO