A novel method to detect translation of membrane proteins following microvesicle intercellular transfer of nucleic acids

Lu, Jie; Pokharel, Deep; Padula, Matthew P.; Bebawy, Mary

doi:10.1093/jb/mvw033

Cited by 7 publications

(8 citation statements)

References 34 publications

(4 reference statements)

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“…As a key component of the cell secretome, microvesicles (MVs) are shed from cell surface by their parental cells into the extracellular environment 17 . Recent reports indicate that these small vesicles can mirror the molecular and functional characteristics of their parental cells and participate in important biological processes 18 , such as the surface-membrane trafficking and the horizontal transfer of proteins and RNAs among neighboring cells 19 , 20 . A growing body of evidences has shown that MVs shed by MSCs (MSC-MVs) express MSC-related markers 21 , 22 , such as CD29, CD44, CD73, CD90, and CD105, which act as key effectors of MSCs.…”

Section: Introductionmentioning

confidence: 99%

Microvesicles as Potential Biomarkers for the Identification of Senescence in Human Mesenchymal Stem Cells

et al. 2017

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Senescence in human mesenchymal stem cells (MSCs) not only contributes to organism aging and the development of a variety of diseases but also severely impairs their therapeutic properties as a promising cell therapy. Studies searching for efficient biomarkers that represent cellular senescence have attracted much attention; however, no single marker currently provides an accurate cell-free representation of cellular senescence. Here, we studied characteristics of MSC-derived microvesicles (MSC-MVs) that may reflect the senescence in their parental MSCs. We found that senescent late passage (LP) MSCs secreted higher levels of MSC-MVs with smaller size than did early passage (EP) MSCs, and the level of CD105+ MSC-MVs decreased with senescence in the parental MSCs. Also, a substantially weaker ability to promote osteogenesis in MSCs was observed in LP than EP MSC-MVs. Comparative analysis of RNA sequencing showed the same trend of decreasing number of highly-expressed miRNAs with increasing number of passages in both MSCs and MSC-MVs. Most of the highly-expressed genes in LP MSCs and the corresponding MSC-MVs were involved in the regulation of senescence-related diseases, such as Alzheimer's disease. Furthermore, based on the miRNA profiling, transcription factors (TF) and genes regulatory networks of MSC senescence, and the datasets from GEO database, we confirmed that expression of miR-146a-5p in MSC-MVs resembled the senescent state of their parental MSCs. Our findings provide evidence that MSC-MVs are a key factor in the senescence-associated secretory phenotype of MSCs and demonstrate that their integrated characteristics can dynamically reflect the senescence state of MSCs representing a potential biomarker for monitoring MSC senescence.

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Section: Introductionmentioning

confidence: 99%

Microvesicles as Potential Biomarkers for the Identification of Senescence in Human Mesenchymal Stem Cells

et al. 2017

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“…MPs are released by various cell types and are involved in many physiological functions such as inflammation, homeostasis, coagulation, chemotherapeutic drug resistance and metastasis [ 2 , 4 , 34 , 49 , 50 , 51 – 55 ]. MPs are established vectors for the cell-to-cell transfer of bioactive molecules including proteins and nucleic acids from their originating cell and mediate intercellular cross talk by transferring functional proteins, nucleic acids, lipids, antigens and cytokines from donor cells to recipient cells [ 48 , 55 – 57 ]. It is not surprising that malignant cells shed a significantly greater number of MP’s in contrast to non-malignant cells [ 2 , 58 ].…”

Section: Role Of Extracellular Vesicles In Transferring P-glycoproteimentioning

confidence: 99%

“…Hence, in cancer patients, the number of circulating MPs as well as their cargo are considerably distinguishable from a healthy patient [ 52 , 53 ]. We were the first to discover a non-genetic pathway contributing to MDR via MP-mediated transfer of functional resistance proteins and nucleic acids from MDR cells to drug-sensitive cells [ 48 , 55 , 59 ] ( Figure 2 ). Specifically, we showed that MPs were spontaneously shed from P-gp and MRP-1 overexpressed MDR leukaemic/breast cancer cells and contain significant amounts of functional resistance proteins (P-gp and MRP1), together with numerous other proteins and nucleic acids that can establish a functional MDR phenotype, increased metastatic capacity and alter the biomechanical properties of recipient cells [ 47 , 55 , 56 , 59 , 60 – 63 ].…”

Section: Role Of Extracellular Vesicles In Transferring P-glycoproteimentioning

confidence: 99%

Proteins regulating the intercellular transfer and function of P-glycoprotein in multidrug-resistant cancer

Pokharel

Roseblade

Oenarto

et al. 2017

ecancer

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Chemotherapy is an essential part of anticancer treatment. However, the overexpression of P-glycoprotein (P-gp) and the subsequent emergence of multidrug resistance (MDR) hampers successful treatment clinically. P-gp is a multidrug efflux transporter that functions to protect cells from xenobiotics by exporting them out from the plasma membrane to the extracellular space. P-gp inhibitors have been developed in an attempt to overcome P-gp-mediated MDR; however, lack of specificity and dose limiting toxicity have limited their effectiveness clinically. Recent studies report on accessory proteins that either directly or indirectly regulate P-gp expression and function and which are necessary for the establishment of the functional phenotype in cancer cells. This review discusses the role of these proteins, some of which have been recently proposed to comprise an interactive complex, and discusses their contribution towards MDR. We also discuss the role of other pathways and proteins in regulating P-gp expression in cells. The potential for these proteins as novel therapeutic targets provides new opportunities to circumvent MDR clinically.

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“…Microparticles (MPs) are a subtype of extracellular vesicle, typically defined as having a size of 0.1-1 μm in diameter, exposure of phosphatidylserine, and the expression of surface antigens originating from their donor cells [68]. MPs also contain functional proteins, second messengers, growth factors, and genetic material from the cell of origin and confer onto recipient cells biological effects [102][103][104][105][106][107][108][109][110][111]. MPs together with exosomes are important cancer biomarkers through their discrete protein and nucleic acid signatures [112].…”

Section: Mirnas Are Important Regulators Of Cancer Mdr and Metastaticmentioning

confidence: 99%

“…Cancer MDR is a significant cause of treatment failure and disease relapse and is attributed to the overexpression of drug efflux transporters belonging to the ATP-binding cassette (ABC) superfamily. MPs can confer MDR through the packaging and intercellular transfer of these functional resistance proteins and nucleic acids from MDR cells to drug-responsive cells [102,104,108,109].…”

Section: Mirnas Are Important Regulators Of Cancer Mdr and Metastaticmentioning

confidence: 99%

Therapeutic prospects of microRNAs in cancer treatment through nanotechnology

Awasthi¹,

Rathbone

Hansbro

et al. 2017

Drug Deliv. and Transl. Res.

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MicroRNAs (miRNAs) represent a new class of diagnostic and prognostic biomarker as well as new therapeutic targets in cancer therapy. miRNAs are gaining significant interest due to extensive advancements in knowledge since their discovery and, more recently, their translational application as therapeutic moieties and targets in the management of disease. miRNAs used in the treatment of cancer would position them as a new class of emerging therapeutic agents. Indeed, numerous candidate miRNAs have been identified as having therapeutic application in the treatment of cancer, but there is still much to learn about how to transform these into effective, patient-compliant, and targeted drug delivery systems. In this mini review, we discuss the utility and potential of nanotechnology in miRNA formulation and delivery with particular emphasis on cancer, including their role in conferring multidrug resistance and metastatic capacity. This review benefits both the formulation and biological scientists in understanding and exploring the new vistas of miRNA delivery using nanotechnology in the cancer clinically.

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A novel method to detect translation of membrane proteins following microvesicle intercellular transfer of nucleic acids

Cited by 7 publications

References 34 publications

Microvesicles as Potential Biomarkers for the Identification of Senescence in Human Mesenchymal Stem Cells

Microvesicles as Potential Biomarkers for the Identification of Senescence in Human Mesenchymal Stem Cells

Proteins regulating the intercellular transfer and function of P-glycoprotein in multidrug-resistant cancer

Therapeutic prospects of microRNAs in cancer treatment through nanotechnology

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