Non-Coding RNAs in Multiple Myeloma Bone Disease Pathophysiology

Raimondi, Lavinia; Luca, Angela De; Giavaresi, Gianluca; Raimondo, Stefania; Gallo, Alessia; Taìana, Elisa; Alessandro, Riccardo; Rossi, Marco; Neri, Antonino; Viglietto, Giuseppe; Amodio, Nicola

doi:10.3390/ncrna6030037

Cited by 12 publications

(13 citation statements)

References 155 publications

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“…Similarly, miR-138 was significatively increased in MM-MSCs compared to HD-MSCs [ 42 ], and inhibition of miR-138 resulted in enhanced osteogenic differentiation of MM-MSCs, being ROCK2, TRPS1, and SULF2 potential miR-138 targets. The expression of other miRNAs has been found upregulated in MM-MSCs (miR-221, miR203a-3p.1, miR-223) or decreased (miR-342, miR-363, or miR-29b) to that of HD-MSCs, modulating the expression of genes involved in osteoblastogenesis (see Raimondi et al [ 43 , 44 ] for reviews).…”

Section: Characterization Of Mesenchymal Stromal Cells In Multiple Myelomamentioning

confidence: 99%

Bone Marrow Mesenchymal Stromal Cells in Multiple Myeloma: Their Role as Active Contributors to Myeloma Progression

Maiso

Mogollón

Ocio

et al. 2021

Cancers

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Multiple myeloma (MM) is a hematological malignancy of plasma cells that proliferate and accumulate within the bone marrow (BM). Work from many groups has made evident that the complex microenvironment of the BM plays a crucial role in myeloma progression and response to therapeutic agents. Within the cellular components of the BM, we will specifically focus on mesenchymal stromal cells (MSCs), which are known to interact with myeloma cells and the other components of the BM through cell to cell, soluble factors and, as more recently evidenced, through extracellular vesicles. Multiple structural and functional abnormalities have been found when characterizing MSCs derived from myeloma patients (MM-MSCs) and comparing them to those from healthy donors (HD-MSCs). Other studies have identified differences in genomic, mRNA, microRNA, histone modification, and DNA methylation profiles. We discuss these distinctive features shaping MM-MSCs and propose a model for the transition from HD-MSCs to MM-MSCs as a consequence of the interaction with myeloma cells. Finally, we review the contribution of MM-MSCs to several aspects of myeloma pathology, specifically to myeloma growth and survival, drug resistance, dissemination and homing, myeloma bone disease, and the induction of a pro-inflammatory and immunosuppressive microenvironment.

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Section: Characterization Of Mesenchymal Stromal Cells In Multiple Myelomamentioning

confidence: 99%

Bone Marrow Mesenchymal Stromal Cells in Multiple Myeloma: Their Role as Active Contributors to Myeloma Progression

Maiso

Mogollón

Ocio

et al. 2021

Cancers

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“…Importantly, miR-29b was found to be downregulated in MM-associated dendritic cells (DCs) as compared to normal mature DCs. Enforcement of miR-29b in DCs co-cultured with MM cells counteracted pro-inflammatory pathways, including STAT3, NF-κB, and various cytokine/chemokine signaling networks, and antagonized DC-induced polarization of T helper lymphocytes into Th17 cells [ 66 , 67 ]. An inflammatory BMM, including DCs, has been reported to promote GI in MM, which in turn promotes the arising of mutations responsible for tumor progression, drug resistance, and immune escape [ 68 ].…”

Section: Non-coding Rna Involvement In MM Gimentioning

confidence: 99%

Genomic Instability in Multiple Myeloma: A “Non-Coding RNA” Perspective

Taìana

Cantafio

Favasuli

et al. 2021

Cancers

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Multiple myeloma (MM) is a complex hematological malignancy characterized by abnormal proliferation of malignant plasma cells (PCs) within a permissive bone marrow microenvironment. The pathogenesis of MM is unequivocally linked to the acquisition of genomic instability (GI), which indicates the tendency of tumor cells to accumulate a wide repertoire of genetic alterations. Such alterations can even be detected at the premalignant stages of monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) and, overall, contribute to the acquisition of the malignant traits underlying disease progression. The molecular basis of GI remains unclear, with replication stress and deregulation of DNA damage repair pathways representing the most documented mechanisms. The discovery that non-coding RNA molecules are deeply dysregulated in MM and can target pivotal components of GI pathways has introduced a further layer of complexity to the GI scenario in this disease. In this review, we will summarize available information on the molecular determinants of GI in MM, focusing on the role of non-coding RNAs as novel means to tackle GI for therapeutic intervention.

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“…Another study found that miR-129-5p, which targeted OBs differentiation markers, was enriched in exosomes from MM patients compared to those from SMM patients, suggesting exosomes may be a useful marker of disease progression (39). Higher expression of exosomal miR-214 detected in osteoporotic patients also suggested exosome's potential as a biomarker for MM bone diseases (34,35). Further validation in other independent MM patient cohorts will explore the potential of circulating exosomal miRNAs to improve the prognostic and risk stratification.…”

Section: Diagnostic and Prognostic Role Of Exosomesmentioning

confidence: 98%

“…Exosomes in the BM have been shown to contribute to this pro-OC microenvironment, resulting in impaired bone formation and MM-related bone disease. Emerging evidence suggests that exosomal ncRNAs play an important role in this regard (34,35).…”

Section: Exosome Impact On Bm Microenvironment Remodelingmentioning

confidence: 99%

Exosomes in the Pathogenesis and Treatment of Multiple Myeloma in the Context of the Bone Marrow Microenvironment

2020

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Multiple myeloma (MM), the second most common hematological malignancy, is an incurable cancer of plasma cells. MM cells diffusely involves the bone marrow (BM) and establish a close interaction with the BM niche that in turn supports MM survival, proliferation, dissemination and drug resistance. In spite of remarkable progress in understanding MM biology and developing drugs targeting MM in the context of the BM niche, acquisition of multi-class drug resistance is almost universally inevitable. Exosomes are small, secreted vesicles that have been shown to mediate bidirectional transfer of proteins, lipids, and nucleic acids between BM microenvironment and MM, supporting MM pathogenesis by promoting angiogenesis, osteolysis, and drug resistance. Exosome content has been shown to differ between MM patients and healthy donors and could potentially serve as both cancer biomarker and target for novel therapies. Furthermore, the natural nanostructure and modifiable surface properties of exosomes make them good candidates for drug delivery or novel immunomodulatory therapy. In this review we will discuss the current knowledge regarding exosome's role in MM pathogenesis and its potential role as a novel biomarker and therapeutic tool in MM.

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Non-Coding RNAs in Multiple Myeloma Bone Disease Pathophysiology

Cited by 12 publications

References 155 publications

Bone Marrow Mesenchymal Stromal Cells in Multiple Myeloma: Their Role as Active Contributors to Myeloma Progression

Bone Marrow Mesenchymal Stromal Cells in Multiple Myeloma: Their Role as Active Contributors to Myeloma Progression

Genomic Instability in Multiple Myeloma: A “Non-Coding RNA” Perspective

Exosomes in the Pathogenesis and Treatment of Multiple Myeloma in the Context of the Bone Marrow Microenvironment

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