scholarly journals Translational Potential of RNA Derived From Extracellular Vesicles in Multiple Myeloma

2021 ◽  
Vol 11 ◽  
Author(s):  
Antonia Reale ◽  
Tiffany Khong ◽  
Sridurga Mithraprabhu ◽  
Andrew Spencer

The cross-talk between tumour cells and stromal cells is a hallmark of multiple myeloma (MM), a blood cancer that still remains incurable despite increased knowledge of its biology and advances in its treatment. Extracellular vesicles (EVs) derived from both tumour and stromal cells have been shown to play an important role in mediating this cross-talk ultimately favouring MM progression and drug resistance. Furthermore, EVs and their content including RNA (EV-RNA) have been successfully isolated from blood and are being explored as liquid biomarkers in MM with the potential to improve diagnosis and monitoring modalities with a minimally-invasive and repeatable analysis, i.e. liquid biopsy. In this review, we describe both the role of EV-RNA in defining the biological features of MM and their potential translational relevance as liquid biomarkers, therapeutic targets and delivery systems. We also discuss the limitations and technical challenges related to the isolation and characterization of EVs and provide a perspective on the future of MM-derived EV-RNA in translational research.

Author(s):  
Sally Yunsun Kim ◽  
Thanh Huyen Phan ◽  
Christina Limantoro ◽  
Bill Kalionis ◽  
Wojciech Chrzanowski

2021 ◽  
Vol 22 (19) ◽  
pp. 10572
Author(s):  
Maria Giovanna Scioli ◽  
Sonia Terriaca ◽  
Elena Fiorelli ◽  
Gabriele Storti ◽  
Giulia Fabbri ◽  
...  

Tumor burden is a complex microenvironment where different cell populations coexist and have intense cross-talk. Among them, a heterogeneous population of tumor cells with staminal features are grouped under the definition of cancer stem cells (CSCs). CSCs are also considered responsible for tumor progression, drug resistance, and disease relapse. Furthermore, CSCs secrete a wide variety of extracellular vesicles (EVs) with different cargos, including proteins, lipids, ssDNA, dsDNA, mRNA, siRNA, or miRNA. EVs are internalized by other cells, orienting the microenvironment toward a protumorigenic and prometastatic one. Given their importance in tumor growth and metastasis, EVs could be exploited as a new therapeutic target. The inhibition of biogenesis, release, or uptake of EVs could represent an efficacious strategy to impair the cross-talk between CSCs and other cells present in the tumor microenvironment. Moreover, natural or synthetic EVs could represent suitable carriers for drugs or bioactive molecules to target specific cell populations, including CSCs. This review will discuss the role of CSCs and EVs in tumor growth, progression, and metastasis and how they affect drug resistance and disease relapse. Furthermore, we will analyze the potential role of EVs as a target or vehicle of new therapies.


2021 ◽  
Author(s):  
T Schlemmer ◽  
L Weipert ◽  
C Preußer ◽  
M Hardt ◽  
A Möbus ◽  
...  

AbstractThe demonstration that spray-induced gene silencing (SIGS) can confer strong disease resistance bypassing the laborious and time-consuming transgenic expression of double-stranded (ds)RNA to induce gene silencing of pathogenic targets was groundbreaking. However, future field applications will require fundamental mechanistic knowledge on dsRNA uptake, processing, and its transfer. There is increasing evidence that extracellular vesicles (EVs) mediate the transfer of transgene-derived small interfering (si)RNAs in host-induced gene silencing (HIGS) applications. Here, we examined the role of EVs regarding the translocation of sprayed dsRNA from barley (Hordeum vulgare) to the target fungusFusarium graminearum. We found barley EVs with 156 nm in size containing predominantly 21 and 19 nucleotide (nt) siRNAs starting with a 5’-terminal Adenine. Notably, barley EVs contain less siRNA compared to EVs isolated from transgenic HIGS Arabidopsis plants. Together our results further underpin mechanistic differences between HIGS and SIGS applications and a minor role of EVs in SIGS.


Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3523
Author(s):  
Wancheng Guo ◽  
Haiqin Wang ◽  
Peng Chen ◽  
Xiaokai Shen ◽  
Boxin Zhang ◽  
...  

Multiple myeloma (MM) is a B-cell tumor of the blood system with high incidence and poor prognosis. With a further understanding of the pathogenesis of MM and the bone marrow microenvironment, a variety of adjuvant cell therapies and new drugs have been developed. However, the drug resistance and high relapse rate of MM have not been fundamentally resolved. Studies have shown that, in patients with MM, there is a type of poorly differentiated progenitor cell (MM stem cell-like cells, MMSCs). Although there is no recognized standard for identification and classification, it is confirmed that they are closely related to the drug resistance and relapse of MM. This article therefore systematically summarizes the latest developments in MMSCs with possible markers of MMSCs, introduces the mechanism of how MMSCs work in MM resistance and recurrence, and discusses the active pathways that related to stemness of MM.


2021 ◽  
Vol 224 (2) ◽  
pp. S75-S76
Author(s):  
Megan Shepherd ◽  
Enkhtuya Radnaa ◽  
Rheanna Urrabaz-Garza ◽  
Talar Kechichian ◽  
Ourlad Alzeus G. Tantengco ◽  
...  

The Analyst ◽  
2016 ◽  
Vol 141 (2) ◽  
pp. 371-381 ◽  
Author(s):  
Vijaya Sunkara ◽  
Hyun-Kyung Woo ◽  
Yoon-Kyoung Cho

We present an overview of current isolation, detection, and characterization methods of extracellular vesicles and their applications and limitations as a potential emerging biomarker in cancer management and their clinical implementation.


Author(s):  
Zezhou Zhao ◽  
Dillon C. Muth ◽  
Vasiliki Mahairaki ◽  
Linzhao Cheng ◽  
Kenneth W. Witwer

1993 ◽  
Vol 340 (1293) ◽  
pp. 325-332 ◽  

Many genes which are regulated by growth factors contain a common regulatory element, the serum response element (SRE). Activation of transcription by the SRE involves a ternary complex formed between a ubiquitous factor, serum response factor (SRF), and a second protein, p62/TCF. We used a yeast genetic screen to isolate cDNAs encoding a protein, SAP-1, with the DNA binding properties of p62/TCF. The SAP-1 sequence contains three regions of homology to the previously uncharacterized Elk-1 protein, which also acts as an SRF accessory protein. Only two of these regions are required for cooperative interactions with SRF in the ternary complex. The third contains several conserved sites for the MAP kinases, whose activity is regulated in response to growth factor stimulation. We discuss the potential role of these proteins in regulation of the c-fos SRE.


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