MiR-29b antagonizes the pro-inflammatory tumor-promoting activity of multiple myeloma-educated dendritic cells

Botta, Cirino; Cucè, Maria; Pitari, Maria Rita; Caracciolo, Daniele; Gullà, Annamaria; Morelli, Eugenio; Riillo, Caterina; Biamonte, Lavinia; Cantafio, Maria Eugenia Gallo; Prabhala, Rao; Mignogna, Chiara; Vito, Anna Di; Altomare, Emanuela; Amodio, Nicola; Martino, Maria Teresa Di; Correale, Pierpaolo; Rossi, Marco; Giordano, Antonio; Munshi, Nikhil C.; Tagliaferri, Pierosandro; Tassone, Pierfrancesco

doi:10.1038/leu.2017.336

Cited by 52 publications

(47 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Following up on the finding on miR-203, researchers have implicated additional miRs in genomic instability in myeloma. Examples include the discovery of a miR-29b-dependent pathway (Botta et al, 2018), the finding that miR-137 induces genomic instability in an aurora kinase A (AURKA)-dependent manner (Qin et al, 2017) and the observation that regulation of DNA ligase III in myeloma involves miR-22 (Caracciolo et al, 2018). No doubt, the list of miRs is poised to expand as the field moves forward and additional RNA species will be tested.…”

Section: Genomic Instability In Myelomamentioning

confidence: 99%

Germline Risk Contribution to Genomic Instability in Multiple Myeloma

et al. 2019

View full text Add to dashboard Cite

Genomic instability, a well-established hallmark of human cancer, is also a driving force in the natural history of multiple myeloma (MM) – a difficult to treat and in most cases fatal neoplasm of immunoglobulin producing plasma cells that reside in the hematopoietic bone marrow. Long recognized manifestations of genomic instability in myeloma at the cytogenetic level include abnormal chromosome numbers (aneuploidy) caused by trisomy of odd-numbered chromosomes; recurrent oncogene-activating chromosomal translocations that involve immunoglobulin loci; and large-scale amplifications, inversions, and insertions/deletions (indels) of genetic material. Catastrophic genetic rearrangements that either shatter and illegitimately reassemble a single chromosome (chromotripsis) or lead to disordered segmental rearrangements of multiple chromosomes (chromoplexy) also occur. Genomic instability at the nucleotide level results in base substitution mutations and small indels that affect both the coding and non-coding genome. Sometimes this generates a distinctive signature of somatic mutations that can be attributed to defects in DNA repair pathways, the DNA damage response (DDR) or aberrant activity of mutator genes including members of the APOBEC family. In addition to myeloma development and progression, genomic instability promotes acquisition of drug resistance in patients with myeloma. Here we review recent findings on the genetic predisposition to myeloma, including newly identified candidate genes suggesting linkage of germline risk and compromised genomic stability control. The role of ethnic and familial risk factors for myeloma is highlighted. We address current research gaps that concern the lack of studies on the mechanism by which germline risk alleles promote genomic instability in myeloma, including the open question whether genetic modifiers of myeloma development act in tumor cells, the tumor microenvironment (TME), or in both. We conclude with a brief proposition for future research directions, which concentrate on the biological function of myeloma risk and genetic instability alleles, the potential links between the germline genome and somatic changes in myeloma, and the need to elucidate genetic modifiers in the TME.

show abstract

Section: Genomic Instability In Myelomamentioning

confidence: 99%

Germline Risk Contribution to Genomic Instability in Multiple Myeloma

et al. 2019

View full text Add to dashboard Cite

show abstract

“…miR-29b was identified in tumor-associated DCs. In this context, miR-29b proved to be upregulated in normal mature DCs and significantly downregulated in tumor-associated DCs [97]. miR-29a and miR-142-3p play a key role in promoting granulopoiesis and monopoiesis and their abnormally decreased expression is responsible for a blockade of blast cell differentiation in some acute myeloid leukemia patients [98].…”

Section: Mirnas Regulating the Role Of Dcs In Inflammatory Responsementioning

confidence: 99%

Role of microRNAs in the Regulation of Dendritic Cell Generation and Function

Scalavino¹,

Liso²,

Serino³

2020

IJMS

View full text Add to dashboard Cite

Dendritic cells (DCs) are antigen-presenting cells with a key role in immune responses. They act as a link between the innate and adaptive systems and they can induce and maintain immunologic tolerance. DCs are subdivided into conventional and plasmacytoid DCs. These cell subsets originate from the same bone marrow precursors and their differentiation process is determined by several extrinsic and intrinsic factors, such as cytokines, transcription factors, and miRNAs. miRNAs are small non-coding RNAs that play a crucial role in modulating physiological and pathological processes mediated by DCs. miRNA deregulation affects many inflammatory conditions and diseases. The aim of this review was to underline the importance of miRNAs in inflammatory processes mediated by DCs in physiological and pathological conditions and to highlight their potential application for future therapies.

show abstract

“…The miRNA network is also dysregulated in MM-associated dendritic cells (DCs) and contributes to their tumor-promoting activity. Enforced expression miR-29b in DCs downregulated IL-23 in PCs also in the context of the SCID-synth-hu model, and antagonized the Th17 inflammatory response, thus restoring an efficient anti-MM immune microenvironment [142]. Preclinical data on other classes of ncRNAs in PC dyscrasias are quite scarce.…”

Section: Sncrnasmentioning

confidence: 99%

The Non-Coding RNA Landscape of Plasma Cell Dyscrasias

Morelli

Gullà

Rocca

et al. 2020

Cancers

View full text Add to dashboard Cite

Despite substantial advancements have been done in the understanding of the pathogenesis of plasma cell (PC) disorders, these malignancies remain hard-to-treat. The discovery and subsequent characterization of non-coding transcripts, which include several members with diverse length and mode of action, has unraveled novel mechanisms of gene expression regulation often malfunctioning in cancer. Increasing evidence indicates that such non-coding molecules also feature in the pathobiology of PC dyscrasias, where they are endowed with strong therapeutic and/or prognostic potential. In this review, we aim to summarize the most relevant findings on the biological and clinical features of the non-coding RNA landscape of malignant PCs, with major focus on multiple myeloma. The most relevant classes of non-coding RNAs will be examined, along with the mechanisms accounting for their dysregulation and the recent strategies used for their targeting in PC dyscrasias. It is hoped these insights may lead to clinical applications of non-coding RNA molecules as biomarkers or therapeutic targets/agents in the near future.

show abstract

MiR-29b antagonizes the pro-inflammatory tumor-promoting activity of multiple myeloma-educated dendritic cells

Cited by 52 publications

References 59 publications

Germline Risk Contribution to Genomic Instability in Multiple Myeloma

Germline Risk Contribution to Genomic Instability in Multiple Myeloma

Role of microRNAs in the Regulation of Dendritic Cell Generation and Function

The Non-Coding RNA Landscape of Plasma Cell Dyscrasias

Contact Info

Product

Resources

About