Hsa_circ_0007841: A novel potential biomarker and drug resistance for multiple myeloma
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ABSTRACT:
PROVIDER: PRJNA549859 | ENA |
REPOSITORIES: ENA
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Project description:Purpose:It has been shown that circular RNA (circRNA) is a key regulatory factor in development and progression of human tumors. However, the working mechanism and clinical significance of most circRNAs remain unknown in human cancer, including multiple myeloma (MM), a hematologic malignancy. Patients and methods:In the present study, high-throughput circRNA microarray was combined with bioinformatics to identify differentially expressed circRNAs in MM. The hsa_circ_0007841 expressions were shown in MM tissues of 86 patients and drug-resistant cell lines and pathological features were detected. Further, the relationship between hsa_circ_0007841 expressions in the MM tissues and pathological features of MM patients were discussed. The role of hsa_circ_0007841 as a potential biomarker and therapeutic target was analyzed. Results:Our results indicated that in MM tissues collected from patients, MM cell lines and drug-resistant cell lines, the hsa_circ_0007841 expression was significantly upregulated. A close connection with prognosis was observed. That is, hsa_circ_0007841 upregulation was correlated with chromosomal aberrations, such as gain 1q21, t(4:14) and mutations in ATR and IRF4 genes. This finding was further verified in large samples. Finally, bioinformatics analysis indicated interaction that 8 differentially expressed miRNAs and 10 candidate mRNAs interacted with hsa_circ_0007841. These results sheds new light on the basic functional research in the future. Conclusion:It was reported for the first time that hsa_circ_0007841 was significantly upregulated in MM. Our study indicated that hsa_circ_0007841 may be a novel biomarker for MM and involved in the progression of MM.
2020-04-10 | GSE133058 | GEO
Project description:1) We identified the genes whose expression was up- and down-regulated by the adhesion to bone marrow stromal cells in human multiple myeloma cell line RPMI8226. 2) We identified the genes whose expression was up- and down-regulated by the PI3K inhibitor PF-04691502 in human multiple myeloma cell line RPMI8226. We isolated mRNA from the multiple myeloma cell line RPMI8226 under drug-resistant conditions, and subjected them to gene expression profiling using an Agilent GeneChip Array.
2015-03-04 | E-GEOD-66466 | biostudies-arrayexpress
Project description:Loss of p53 enhances the tumor-initiating potential and drug resistance of clonogenic multiple myeloma cells
| PRJNA900292 | ENA
Project description:Multiple myeloma (MM) is a life-threatening, chronic, and incurable hematological malignancy, which is characterized by clonal proliferation of malignant plasma cells. Despite recent therapeutic advances, relapse is very common during a long-term exposure to drugs with no therapeutic effects. Here, we conducted longitudinal single-cell transcriptome sequencing (scRNA-seq) of bone marrow cells from a single patient with relapsed and refractory MM, who had been treated with multiple anti-myeloma drugs, and found five UMAP subclusters (clusters 0-4) of MM cells, which appeared and/or disappeared in response to the therapeutic pressure. A small cell cluster 3, which emerged during lenalidomide treatment and disappeared after the addition of a proteasome inhibitor (PI), ixazomib. Among the differentially expressed genes in cluster 3, we found a candidate drug-response gene; pellino E3 ubiquitin protein ligase family member 2 (PELI2), which is responsible for PI-induced cell death in in vitro cell cultured assay. Kaplan-Meier survival analysis of datasets from pan-cancer prognostic database revealed that higher expression of PELI2 is associated with better prognosis. The data of this study suggest that PELI2 is a predictive biomarker of the PI response in patients with MM. Our integrated strategy combining longitudinal scRNA-seq analysis, in vitro functional assay, and database analysis would facilitate the understanding of clonal dynamics of MM in response to anti-myeloma drugs and identification of drug response genes.
2022-08-18 | GSE193695 | GEO
Project description:Proteasome inhibitors are important chemotherapeutics in the treatment of multiple myeloma, but they are currently used empirically as no markers of sensitivity have been validated. We have identified expression of tight junction protein (TJP) 1 as being associated with sensitivity of plasma cells in vitro and in vivo to proteasome inhibitors. TJP1 suppressed expression of genes in the major histocompatibility class II region, including two catalytically active immunoproteasome subunits, thereby decreasing proteasome activity, a critical determinant of proteasome inhibitor sensitivity. This occurred through suppression by TJP1 of signaling through the epidermal growth factor receptor/Janus kinase 1/signal transducer and activator of transcription 3 pathway. In the clinic, high TJP1 expression in myeloma patients was associated with a significantly higher likelihood of responding to bortezomib, and with a longer time-to-progression after treatment. Taken together, these data support the use of TJP1 as a biomarker of sensitivity and resistance to proteasome inhibitors. To further elucidate mechanisms of bortezomib resistance, we developed human-derived multiple myeloma cell lines with a 4-fold or greater resistance to bortezomib. Then total RNA for bortezomib resistant (BR) and wild type (WT) was extracted and used for comparison by gene expression profiling.
2015-12-31 | E-GEOD-52369 | biostudies-arrayexpress
Project description:Multiple myeloma (MM) remains incurable due to drug resistance. Ribosomal protein S3 (RPS3) has been identified as a non-Rel subunit of NF-κB. However, the detailed biological roles of RPS3 remain unclear. Here, we report for the first time that RPS3 is necessary for MM survival and drug resistance. RPS3 was highly expressed in MM, and knockout of RPS3 in MM inhibited cell growth and induced cell apoptosis both in vitro and in vivo. Overexpression of RPS3 mediated the proteasome inhibitor resistance of MM and delayed the survival of MM tumour-bearing animals. Moreover, our present study found an interaction between RPS3 and the thyroid hormone receptor interactor 13 (TRIP13), an oncogene related to MM tumorigenesis and drug resistance. We demonstrated that the phosphorylation of RPS3 was mediated by TRIP13 via PKCδ, which played an important role in activating the canonical NF-κB signalling and inducing cell survival and drug resistance in MM. Notably, the inhibition of NF-κB signalling by the small-molecule inhibitor targeting TRIP13, DCZ0415, was capable of triggering synergistic cytotoxicity when combined with bortezomib in drug-resistant MM. This study identifies RPS3 as a novel biomarker and therapeutic target in MM.
2023-08-18 | GSE240978 | GEO
Project description:Transcriptional heterogeneity overcomes super-enhancer disrupting drug combinations in multiple myeloma
| PRJNA1020864 | ENA
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