miRNA-seq and clinical evaluation in multiple myeloma: miR-181a overexpression predicts short-term disease progression and poor post-treatment outcome

Papadimitriou, M.; Παπανώτα, Αριστέα-Μαρία; Adamopoulos, Panagiotis G.; Pilala, Katerina-Marina; Liacos, Christine‐Ivy; Malandrakis, Panagiotis; Mavrianou-Koutsoukou, Nefeli; Patseas, Dimitrios; Eleutherakis‐Papaiakovou, Evangelos; Gavriatopoulou, Maria; Kastritis, Efstathios; Avgeris, Margaritis; Dimopoulos, Meletios Α.; Terpos, Evangelos; Scorilas, Andreas

doi:10.1038/s41416-021-01602-8

Cited by 13 publications

(8 citation statements)

References 59 publications

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“…This technology has made a huge contribution to some niche diseases. For example: neuropsychiatric diseases [22], multiple myeloma [23], glucocorticoid-induced osteoporosis [24], etc. However, to date, there have been few reports using this method to study the pathogenesis of hearing loss.…”

Section: Discussionmentioning

confidence: 99%

Transcriptome sequencing of PBMC reveals Hsa-miR-124-5p regulates cell cycle and metabolism of lipids via targeting CSTF2/ TXNRD1 in hearing loss patients

Zhang

Sun

Cong

et al. 2022

Preprint

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BackgroundHearing loss (HL) is a public health event, which seriously affects the happiness of people’s life. Hsa-miR-124-5p has not been reported in HL. This study aimed to construct a miRNA-mRNA network associated with HL.MethodsSubjects were screened through clinical audiology experiments. MiRNA-seq was performed on the peripheral blood mononuclear cells (PBMC), and the differentially expressed miRNAs (DEMs, P-Value < 0.05, ∣log FC | ≥1) were obtained by analysis. We selected the most significantly up-regulated DEMs for research. We predicted the downstream target genes of the most significantly up-regulated DEMs through miRDB, mirDIP, mirtarbase and TargetScan databases, and four database overlapping genes were considered as downstream target genes. Enrichment analysis was performed on overlapping genes. Then, a protein-protein interaction (PPI) network of overlapping genes was performed through STRING database, aimed to pick out hub genes. Finally, we construct the miRNA-mRNA network.ResultsThere were 6 clinical participants, 3 hearing loss patients and 3 healthy subjects.There are 29 DEMs, of which hsa-miR-124-5p is the most significantly up-regulated DEMs. 13 downstream target genes corresponding to hsa-miR-124-5p were screened, which were significantly enriched in cell cycle and metabolism of lipids. PPI analysis was performed on 13 target genes, and two hub genes (CSTF2/ TXNRD1) were finally obtained. Most importantly, miRNA-mRNA networks containing hsa-miR-124-5p/CSTF2 and hsa-miR-124-5p/TXNRD1 were successfully constructed.ConclusionsIn summary, hsa-miR-124-5p may be a novel biomarker for hearing loss patients and play a important role in hearing loss patients by targeting CSTF2 and TXNRD1. Hsa-miR-124-5p may participate in cell cycle and metabolism of lipids biological process in hearing loss patients.

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Section: Discussionmentioning

confidence: 99%

Transcriptome sequencing of PBMC reveals Hsa-miR-124-5p regulates cell cycle and metabolism of lipids via targeting CSTF2/ TXNRD1 in hearing loss patients

Zhang

Sun

Cong

et al. 2022

Preprint

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“…It has been reported that miRNA-181 is overexpressed in CD138 + PCs from MM patients [ 9 , 77 ]. miR-181 is released to BME by BMSC-derived exosomes and may be uptaken by PCs [ 78 ].…”

Section: Bm Tumor Microenvironment and The Critical Reactions In Mult...mentioning

confidence: 99%

Exosomal miRNAs in the Tumor Microenvironment of Multiple Myeloma

Alipoor

Chang

2023

Cells

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Multiple myeloma (MM) is a malignancy of plasma cells in the bone marrow and is characterized by the clonal proliferation of B-cells producing defective monoclonal immunoglobulins. Despite the latest developments in treatment, drug resistance remains one of the major challenges in the therapy of MM. The crosstalk between MM cells and other components within the bone marrow microenvironment (BME) is the major determinant of disease phenotypes. Exosomes have emerged as the critical drivers of this crosstalk by allowing the delivery of informational cargo comprising multiple components from miniature peptides to nucleic acids. Such material transfers have now been shown to perpetuate drug-resistance development and disease progression in MM. MicroRNAs(miRNAs) specifically play a crucial role in this communication considering their small size that allows them to be readily packed within the exosomes and widespread potency that impacts the developmental trajectory of the disease inside the tumor microenvironment (TME). In this review, we aim to provide an overview of the current understanding of the role of exosomal miRNAs in the epigenetic modifications inside the TME and its pathogenic influence on the developmental phenotypes and prognosis of MM.

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“…Several studies have identified circulating miRNAs in serum and plasma as predictors of progression-free survival (PFS) and OS in myeloma [12,13], but the cellular sources of circulating miRNAs are largely unknown. Among endogenously expressed miRNAs from primary myeloma cells, miR-15a, miR-33b, miR-17, miR-886-5p and miR-181a have been identified as prognostic factors by qPCR-and microarray-based methods [14][15][16]. These survival-associated miRNAs were identified after being detected as differentially expressed in multiple myeloma or between ISS subgroups and significance was not adjusted for multiple testing across all expressed miRNAs in the cell.…”

Section: Introductionmentioning

confidence: 99%

Comprehensive small RNA-sequencing of primary myeloma cells identifies miR-105-5p as a predictor of patient survival

et al. 2022

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Background Small RNAs (sRNAs), a heterogenous group of non-coding RNAs, are emerging as promising molecules for cancer patient risk stratification and as players in tumour pathogenesis. Here, we have studied microRNAs (miRNAs) and other sRNAs in relation to survival and disease severity in multiple myeloma. Methods We comprehensively characterised sRNA expression in multiple myeloma patients by performing sRNA-sequencing on myeloma cells isolated from bone marrow aspirates of 86 myeloma patients. The sRNA expression profiles were correlated with the patients’ clinical data to investigate associations with survival and disease subgroups, by using cox proportional hazards (coxph) -models and limma-voom, respectively. A publicly available sRNA dataset was used as external validation (n = 151). Results We show that multiple miRNAs are differentially expressed between ISS Stage I and III. Interestingly, we observed the downregulation of seven different U2 spliceosomal RNAs, a type of small nuclear RNAs in severe disease stages. Further, by a discovery-based approach, we identified miRNA miR-105-5p as a predictor of poor overall survival (OS) in multiple myeloma. Multivariate analysis showed that miR-105-5p predict OS independently of established disease markers. Conclusions Overexpression of miR-105-5p in myeloma cells correlates with reduced OS, potentially improving prognostic risk stratification in multiple myeloma.

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miRNA-seq and clinical evaluation in multiple myeloma: miR-181a overexpression predicts short-term disease progression and poor post-treatment outcome

Cited by 13 publications

References 59 publications

Transcriptome sequencing of PBMC reveals Hsa-miR-124-5p regulates cell cycle and metabolism of lipids via targeting CSTF2/ TXNRD1 in hearing loss patients

Transcriptome sequencing of PBMC reveals Hsa-miR-124-5p regulates cell cycle and metabolism of lipids via targeting CSTF2/ TXNRD1 in hearing loss patients

Exosomal miRNAs in the Tumor Microenvironment of Multiple Myeloma

Comprehensive small RNA-sequencing of primary myeloma cells identifies miR-105-5p as a predictor of patient survival

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