MicroRNAs as a Potential New Preventive Approach in the Transition from Asymptomatic to Symptomatic Multiple Myeloma Disease

Desantis, Vanessa; Solimando, Antonio Giovanni; Saltarella, Ilaria; Sacco, Antonio; Giustini, Viviana; Bento, Marta Leal; Lamanuzzi, Aurelia; Melaccio, Assunta; Frassanito, Maria Antonia; Paradiso, Angelo; Montagnani, Monica; Vacca, Angelo; Roccaro, Aldo M.

doi:10.3390/cancers13153650

Cited by 16 publications

(18 citation statements)

References 107 publications

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“…Low levels of let-7e, miR-223-3p and miR-744 were associated with shorter remission and OS in MM patients [ 147 , 148 ], while up-regulation of miR-720 and miR-1246 correlated with shorter PFS data [ 149 ].…”

Section: Clinical Applications Of Mirnas Focusing On Hematological Ma...mentioning

confidence: 99%

Implication of microRNAs in Carcinogenesis with Emphasis on Hematological Malignancies and Clinical Translation

Gaál

2022

IJMS

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MicroRNAs (miRNAs) are evolutionarily conserved small non-coding RNAs, that are involved in the multistep process of carcinogenesis, contributing to all established hallmarks of cancer. In this review, implications of miRNAs in hematological malignancies and their clinical utilization fields are discussed. As components of the complex regulatory network of gene expression, influenced by the tissue microenvironment and epigenetic modifiers, miRNAs are “micromanagers” of all physiological processes including the regulation of hematopoiesis and metabolic pathways. Dysregulated miRNA expression levels contribute to both the initiation and progression of acute leukemias, the metabolic reprogramming of malignantly transformed hematopoietic precursors, and to the development of chemoresistance. Since they are highly stable and can be easily quantified in body fluids and tissue specimens, miRNAs are promising biomarkers for the early detection of hematological malignancies. Besides novel opportunities for differential diagnosis, miRNAs can contribute to advanced chemoresistance prediction and prognostic stratification of acute leukemias. Synthetic oligonucleotides and delivery vehicles aim the therapeutic modulation of miRNA expression levels. However, major challenges such as efficient delivery to specific locations, differences of miRNA expression patterns between pediatric and adult hematological malignancies, and potential side effects of miRNA-based therapies should be considered.

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Section: Clinical Applications Of Mirnas Focusing On Hematological Ma...mentioning

confidence: 99%

Implication of microRNAs in Carcinogenesis with Emphasis on Hematological Malignancies and Clinical Translation

Gaál

2022

IJMS

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“…Several studies support the function of miRNA as tumour suppressors [ 55 ], e.g., miR-34 represses tumour progression through epithelial-mesenchymal transition (EMT) via EMT-transcription factors when dysregulated via the synergistic effect of the p53 tumor suppressor gene and some important signal pathways. Several invitro studies on various cancer cell lines found that through different signalling pathways downregulation of the family of miR-34 can lead to colon, prostate, lung, osteosarcoma, and other types of cancers [ 54 , 55 , 56 , 57 , 58 , 59 ]. Similarly, Pichiorri et al found the overexpression of miR-106b∼25 cluster, miR-181a and b and miR-21 in MM cell lines leading to the tumour compared to normal cell controls thus acting as an oncogene when two miRNA cluster.…”

Section: Mirnas—biogenesis Biochemistry and Functionsmentioning

confidence: 99%

“…Similarly, Pichiorri et al found the overexpression of miR-106b∼25 cluster, miR-181a and b and miR-21 in MM cell lines leading to the tumour compared to normal cell controls thus acting as an oncogene when two miRNA cluster. In contrast, miRNA-106b, miRNA-181a and b were found to be deregulated, thus acting as tumour suppressors [ 58 ].…”

Section: Mirnas—biogenesis Biochemistry and Functionsmentioning

confidence: 99%

“…Multiple myeloma is a cancer of the bone marrow, affecting various parts of the body. Several studies reported that the association of the disease progression or stages involves circulating miRNA [ 58 ], e.g., the combination of miRNA-720 and -1308 can be helpful in distinguishing a Healthy Donor from Multiple myeloma patients. Moreover, the association of miRNA-1246 and MiRNA-1308 can be helpful in determining monoclonal gammopathy of undetermined significance (MGUS) from the MM condition [ 105 ].…”

Section: Mirnas—biogenesis Biochemistry and Functionsmentioning

confidence: 99%

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miRNAs in the Regulation of Cancer Immune Response: Effect of miRNAs on Cancer Immunotherapy

Pottoo

Iqubal

et al. 2021

Cancers

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In the last few decades, carcinogenesis has been extensively explored and substantial research has identified immunogenic involvement in various types of cancers. As a result, immune checkpoint blockers and other immune-based therapies were developed as novel immunotherapeutic strategies. However, despite being a promising therapeutic option, immunotherapy has significant constraints such as a high cost of treatment, unpredictable toxicity, and clinical outcomes. miRNAs are non-coding, small RNAs actively involved in modulating the immune system’s multiple signalling pathways by binding to the 3′-UTR of target genes. miRNAs possess a unique advantage in modulating multiple targets of either the same or different signalling pathways. Therefore, miRNA follows a ‘one drug multiple target’ hypothesis. Attempts are made to explore the therapeutic promise of miRNAs in cancer so that it can be transported from bench to bedside for successful immunotherapeutic results. Therefore, in the current manuscript, we discussed, in detail, the mechanism and role of miRNAs in different types of cancers relating to the immune system, its diagnostic and therapeutic aspect, the effect on immune escape, immune-checkpoint molecules, and the tumour microenvironment. We have also discussed the existing limitations, clinical success and the prospective use of miRNAs in cancer.

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“…Although gene expression profiles focusing on coding genes provide valuable insight into cell development and malignant transformation, protein-coding genes account for less than 3% of the human genome, with over 70% of the genome being transcribed into non-coding RNAs (ncRNAs) [11], leading to intensive investigations into potential functional roles for ncRNAs. Indeed, both small non-coding micro-RNAs (miRNAs) and long non-coding RNAs (lncRNAs) have been shown to play important roles in many processes including B cell development and malignancy including multiple myeloma (MM), a plasma cell dyscrasia (reviewed in [12][13][14][15][16]). Furthermore, there is a growing recognition of the integral role that ncRNAs play in both Ig gene rearrangement and class switch recombination [17][18][19], underscoring the need to more completely identify patterns of ncRNA expression that occur during B cell activation, proliferation, and differentiation into PCs.…”

Section: Introductionmentioning

confidence: 99%

Stage-Specific Non-Coding RNA Expression Patterns during In Vitro Human B Cell Differentiation into Antibody Secreting Plasma Cells

Tschumper

Hoelzinger

Walters

et al. 2022

ncRNA

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The differentiation of B cells into antibody secreting plasma cells (PCs) is governed by a strict regulatory network that results in expression of specific transcriptomes along the activation continuum. In vitro models yielding significant numbers of PCs phenotypically identical to the in vivo state enable investigation of pathways, metabolomes, and non-coding (ncRNAs) not previously identified. The objective of our study was to characterize ncRNA expression during human B cell activation and differentiation. To achieve this, we used an in vitro system and performed RNA-seq on resting and activated B cells and PCs. Characterization of coding gene transcripts, including immunoglobulin (Ig), validated our system and also demonstrated that memory B cells preferentially differentiated into PCs. Importantly, we identified more than 980 ncRNA transcripts that are differentially expressed across the stages of activation and differentiation, some of which are known to target transcription, proliferation, cytoskeletal, autophagy and proteasome pathways. Interestingly, ncRNAs located within Ig loci may be targeting both Ig and non-Ig-related transcripts. ncRNAs associated with B cell malignancies were also identified. Taken together, this system provides a platform to study the role of specific ncRNAs in B cell differentiation and altered expression of those ncRNAs involved in B cell malignancies.

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MicroRNAs as a Potential New Preventive Approach in the Transition from Asymptomatic to Symptomatic Multiple Myeloma Disease

Cited by 16 publications

References 107 publications

Implication of microRNAs in Carcinogenesis with Emphasis on Hematological Malignancies and Clinical Translation

Implication of microRNAs in Carcinogenesis with Emphasis on Hematological Malignancies and Clinical Translation

miRNAs in the Regulation of Cancer Immune Response: Effect of miRNAs on Cancer Immunotherapy

Stage-Specific Non-Coding RNA Expression Patterns during In Vitro Human B Cell Differentiation into Antibody Secreting Plasma Cells

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