The research of RBM39 in multiple myeloma
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo Sapiens
SUBMITTER: 
Hua Yan
PROVIDER: PXD060610 | iProX | Sun Feb 09 00:00:00 GMT 2025
REPOSITORIES: iProX
Publications
Targeting the RBM39-MEK5 axis synergizes with bortezomib to inhibit the malignant growth of multiple myeloma.
Liu Jia J Zhang Zilu Z Xu Wenbin W Jia Mingyuan M Zeng Xinyi X Wu Chengyu C Fu Ze Z Xu Xiaoguang X Ye Chenjing C Wu Chao C Xu Hanzhang H Lei Hu H Wu Yingli Y Yan Hua H
Blood advances 20250401 8
<h4>Abstract</h4>Aberrant alternative splicing is one of the hallmarks of cancer and is potentially based on upregulated expression-of-splicing factors in some types of cancer. Our previous study suggested that the splicing factor RBM39 is significantly upregulated in multiple myeloma (MM) and that its upregulation is positively associated with poor prognosis. Here, we further demonstrate that the survival and proliferation of MM cells rely on RBM39 and that RBM39 knockdown inhibits the malignan ...[more]
Similar Datasets
Project description:<h4><strong>BACKGROUND:</strong> Multiple myeloma is characterized by clonal proliferation of malignant plasma cells in the bone marrow that produce monoclonal immunoglobulins. N-glycosylation changes of these monoclonal immunoglobulins have been reported in multiple myeloma, but previous studies only detected limited serum N-glycan features.</h4><h4><strong>METHODS:</strong> Here, a more detailed study of the human serum N-glycome of 91 multiple myeloma patients and 51 controls was performed. We additionally analyzed sequential samples from patients (n = 7) which were obtained at different time points during disease development as well as 16 paired blood serum and bone marrow plasma samples. N-glycans were enzymatically released and measured by mass spectrometry after linkage specific derivatization of sialic acids.</h4><h4><strong>RESULTS:</strong> A decrease in both α2,3- and α2,6-sialylation, galactosylation and an increase in fucosylation within complex-type N-glycans were found in multiple myeloma patients compared to controls, as well as a decrease in difucosylation of diantennary glycans. The observed glycosylation changes were present in all ISS stages, including the 'low-risk' ISS I. In individual patients, difucosylation of diantennary glycans decreased with development of the disease. Protein N-glycosylation features from blood and bone marrow showed strong correlation. Moreover, associations of monoclonal immunoglobulin (M-protein) and albumin levels with glycan traits were discovered in multiple myeloma patients.</h4><h4><strong>CONCLUSIONS & GENERAL SIGNIFICANCE: </strong>In conclusion, serum protein N-glycosylation analysis could successfully distinguish multiple myeloma from healthy controls. Further studies are needed to assess the potential roles of glycan trait changes and the associations of glycans with clinical parameters in multiple myeloma early detection and prognosis.</h4>
2022-04-27 | MTBLS676 | MetaboLights
Project description:The paper describes a model of multiple myeloma.
Created by COPASI 4.26 (Build 213)
This model is described in the article:
A mathematical model of cell equilibrium and joint cell formation in multiple myeloma
M.A. Koenders, R. Saso
Journal of Theoretical Biology 390 (2016) 73–79
Abstract:
In Multiple Myeloma Bone Disease healthy bone remodelling is affected by tumour cells by means of paracrine cytokinetic signalling in such a way that osteoclast formation is enhanced and the growth of osteoblast cells inhibited. The participating cytokines are described in the literature. Osteoclast-induced myeloma cell growth is also reported. Based on existing mathematical models for healthy bone remo- delling a three-way equilibrium model is presented for osteoclasts, osteoblasts and myeloma cell populations to describe the progress of the illness in a scenario in which there is a secular increase in the cytokinetic interactive effectiveness of paracrine processes. The equilibrium state for the system is obtained. The paracrine interactive effectiveness is explored by parameter variation and the stable region in the parameter space is identified. Then recently-discovered joint myeloma–osteoclast cells are added to the model to describe the populations inside lytic lesions. It transpires that their presence expands the available parameter space for stable equilibrium, thus permitting a detrimental, larger population of osteoclasts and myeloma cells. A possible relapse mechanism for the illness is explored by letting joint cells dissociate. The mathematics then permits the evaluation of the evolution of the cell populations as a function of time during relapse.
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To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide.
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2024-09-02 | BIOMD0000000804 | BioModels
Project description:To investigate the role of HAPLN1 in multiple myeloma, we treated RPMI8226 multiple myeloma cells with recombinant HAPLN1-PTR1. We then performed gene expression profiling analysis using data obtained from RNA-seq.
2022-09-06 | GSE202672 | GEO
Project description:To identify the HAPLN1-induced genes regulated by STAT1 in multiple myeloma, we treated RPMI8226 multiple myeloma cells (WT or STAT1 KO) with recominant HAPLN1-PTR1. We then performed gene expression profiling analysis using data obtained from RNA-seq.
2023-12-06 | GSE237216 | GEO
Project description:Multiple myeloma is a plasma cell malignancy of the bone marrow. Despite therapeutic advances, multiple myeloma remains incurable and better risk stratification as well as new therapies are therefore highly needed. The proteome of multiple myeloma has not been systematically assessed before and holds the potential to uncover additional insight into disease biology and improved prognostic models. Here, we provide a comprehensive multi-omics analysis including deep tandem mass tag (TMT)-based quantitative global (phospho)proteomics, RNA sequencing and nanopore DNA sequencing of 138 primary patient-derived plasma cell malignancies encompassing treatment-naive multiple myeloma patients treated in clinical trials, plasma cell leukemia, and the premalignancy monoclonal gammopathy of undetermined significance (MGUS), as well as healthy controls. We found that the (phospho)proteome of malignant plasma cells is highly deregulated as compared to healthy plasma cells and is both defined by chromosomal alterations and extensive post-transcriptional regulation. A protein signature was identified that is associated with aggressive disease and more predictive for outcome than cytogenetic-based risk assessment in newly diagnosed multiple myeloma. Integration with functional genetics and single-cell sequencing revealed generally and genetic subtype-specific deregulated proteins and pathways in plasma cell malignancies that include novel potential targets for (immuno)therapies. These findings provide new insights in the biology of multiple myeloma and will be a unique resource for investigating new therapeutic approaches.
2024-07-09 | PXD043580 | Pride
Project description:Multiple myeloma is a plasma cell malignancy of the bone marrow. Despite therapeutic advances, multiple myeloma remains incurable and better risk stratification as well as new therapies are therefore highly needed. The proteome of multiple myeloma has not been systematically assessed before and holds the potential to uncover additional insight into disease biology and improved prognostic models. Here, we provide a comprehensive multi-omics analysis including deep tandem mass tags (TMT)-based quantitative global (phospho)proteomics, RNA sequencing and nanopore DNA sequencing of 138 primary patient-derived plasma cell malignancies encompassing treatment-naive multiple myeloma patients treated in clinical trials, plasma cell leukemia, and the premalignancy monoclonal gammopathy of undetermined significance (MGUS), as well as healthy controls. We found that the (phospho)proteome of malignant plasma cells is highly deregulated as compared to healthy plasma cells and is both defined by chromosomal alterations and extensive post-transcriptional regulation. A protein signature was identified that is associated with aggressive disease and more predictive for outcome than cytogenetic-based risk assessment in newly diagnosed multiple myeloma. Integration with functional genetics and single-cell sequencing revealed generally and genetic subtype-specific deregulated proteins and pathways in plasma cell malignancies that include novel potential targets for (immuno)therapies. These findings provide new insights in the biology of multiple myeloma and will be a unique resource for investigating new therapeutic approaches.
2024-07-09 | PXD038437 | Pride
Project description:<p>The Multiple Myeloma Research Foundation (MMRF) CoMMpass (Relating <u>C</u>linical <u>O</u>utcomes in <u>MM</u> to <u>P</u>ersonal <u>Ass</u>essment of Genetic Profile) trial (NCT01454297) is a longitudinal observation study of 1000 newly diagnosed myeloma patients receiving various standard approved treatments that aim at collecting tissue samples, genetic information, Quality of Life (QoL) and various disease and clinical outcomes over 10 years.</p>
| phs000748 | dbGaP
Project description:We report the microRNA expression in patients with multiple myeloma and healthy adults. RNA sequencing was performed for circulating exosomes obtained from the serum of 10 MM patients and 5 healthy individuals.
2017-08-22 | GSE94564 | GEO
Project description:Purpose: Multiple myeloma is a malignancy of plasma cells. Extensive genetic and transcriptional characterization of myeloma has identified subtypes with prognostic and therapeutic implications. In contrast, relatively little is known about the myeloma epigenome. Experimental Design: CD138+CD38+ myeloma cells were isolated from fresh bone marrow aspirate or the same aspirate after freezing for one to six months. Gene expression and chromatin accessibility were compared between fresh and frozen samples by RNA-seq and ATAC-seq. Chromatin accessible regions were used to identify regulatory RNA expression in over 700 samples from newly diagnosed patients in the MMRF CoMMpass trial (NCT01454297). Results: Gene expression and chromatin accessibility of cryopreserved myeloma recapitulated that of freshly isolated samples. ATAC-seq performed on a series of biobanked specimens identified thousands of chromatin accessible regions with hundreds being highly coordinated with gene expression. Over 4,700 of these chromatin accessible regions were transcribed in newly diagnosed myelomas from the CoMMpass trial. Regulatory element activity alone recapitulated myeloma gene expression subtypes, and in particular myeloma subtypes with IGH translocations were defined by transcription of distal regulatory elements. Moreover, enhancer activity predicted oncogene expression implicating gene regulatory mechanisms in aggressive myeloma. Conclusions: These data demonstrate the feasibility of using biobanked specimens for retrospective studies of the myeloma epigenome and illustrate the unique enhancer landscapes of myeloma subtypes that are coupled to gene expression and disease progression.
2021-03-03 | GSE167967 | GEO