Exosomal noncoding RNAs: key players in glioblastoma drug resistance

Movahedpour, Ahmad; Khatami, Seyyed Hossein; Khorsand, Marjan; Salehi, Mahsa; Savardashtaki, Amir; Mirmajidi, Seyedeh Habibeh; Negahdari, Babak; Khanjani, Nezhat; Naeli, Parisa; Vakili, Omid; Taheri‐Anganeh, Mortaza

doi:10.1007/s11010-021-04221-2

Cited by 39 publications

(25 citation statements)

References 123 publications

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“…Our NanoString data showed that there were at least 25 highly expressed miRNAs in all three GSC lines and that 8 of the 25 miRNAs (mir320e, mir520f-3p, mir363-3p, mir144-4p, mir16-5p, mir495-3p, mir23a-3p, mir155-5p) have a seed sequence to target PTEN, whilst 3 of the 25 miRNAs (mir612, mir142-3p, mir551a) were found to be common in the Glioblastoma Bio Discovery Portal of the TCGA database. This is in line with previous publications showing that miRNAs packaged within EVs can modulate the intercellular communications within the brain microenvironment [ 15 , 50 , 51 , 52 ], as well as playing a role in how the tumour responds to therapy [ 53 ]. There were many abundantly expressed miRNAs found in the EVs of T98G cells subjected to invasion [ 51 ] and serum EVs [ 52 ] involved in glioma progression [ 54 ], yet only a few miRNAs were found in common with our study, expressing at low levels ( Supplementary Table S2 ).…”

Section: Discussionsupporting

confidence: 91%

Extracellular Vesicles Secreted by Glioma Stem Cells Are Involved in Radiation Resistance and Glioma Progression

Nguyen

Jones

et al. 2022

IJMS

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Glioblastoma is the most aggressive brain tumour with short survival, partly due to resistance to conventional therapy. Glioma stem cells (GSC) are likely to be involved in treatment resistance, by releasing extracellular vesicles (EVs) containing specific molecular cargoes. Here, we studied the EVs secreted by glioma stem cells (GSC-EVs) and their effects on radiation resistance and glioma progression. EVs were isolated from 3 GSCs by serial centrifugation. NanoSight measurement, cryo-electron microscopy and live imaging were used to study the EVs size, morphology and uptake, respectively. The non-GSC glioma cell lines LN229 and U118 were utilised as a recipient cell model. Wound healing assays were performed to detect cell migration. Colony formation, cell viability and invadopodium assays were conducted to detect cell survival of irradiated recipient cells and cell invasion post GSC-EV treatment. NanoString miRNA global profiling was used to select for the GSC-EVs’ specific miRNAs. All three GSC cell lines secreted different amounts of EVs, and all expressed consistent levels of CD9 but different level of Alix, TSG101 and CD81. EVs were taken up by both LN229 and U118 recipient cells. In the presence of GSC-EVs, these recipient cells survived radiation exposure and initiated colony formation. After GSC-EVs exposure, LN229 and U118 cells exhibited an invasive phenotype, as indicated by an increase in cell migration. We also identified 25 highly expressed miRNAs in the GSC-EVs examined, and 8 of these miRNAs can target PTEN. It is likely that GSC-EVs and their specific miRNAs induced the phenotypic changes in the recipient cells due to the activation of the PTEN/Akt pathway. This study demonstrated that GSC-EVs have the potential to induce radiation resistance and modulate the tumour microenvironment to promote glioma progression. Future therapeutic studies should be designed to interfere with these GSC-EVs and their specific miRNAs.

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Section: Discussionsupporting

confidence: 91%

Extracellular Vesicles Secreted by Glioma Stem Cells Are Involved in Radiation Resistance and Glioma Progression

Nguyen

Jones

et al. 2022

IJMS

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“…Exosomes secreted by both tumor and stromal cells play an integral role in treating resistance because of their nature as mediators of intercellular communication (77). Moreover, it has been suggested that the key exosomal miRNA could target diverse signaling pathways or affect regulatory proteins and their corresponding genes, thereupon modulating GBM drug resistance (78). Exploring the machinery of treatment resistance is relevant for eliminating these aggressive tumors.…”

Section: Exosomal Mirnas and Treatment Resistance Of Gliomamentioning

confidence: 99%

Current Understanding of Exosomal MicroRNAs in Glioma Immune Regulation and Therapeutic Responses

Peng

Liang

et al. 2022

Front. Immunol.

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Exosomes, the small extracellular vesicles, are released by multiple cell types, including tumor cells, and represent a novel avenue for intercellular communication via transferring diverse biomolecules. Recently, microRNAs (miRNAs) were demonstrated to be enclosed in exosomes and therefore was protected from degradation. Such exosomal miRNAs can be transmitted to recipient cells where they could regulate multiple cancer-associated biological processes. Accumulative evidence suggests that exosomal miRNAs serve essential roles in modifying the glioma immune microenvironment and potentially affecting the malignant behaviors and therapeutic responses. As exosomal miRNAs are detectable in almost all kinds of biofluids and correlated with clinicopathological characteristics of glioma, they might be served as promising biomarkers for gliomas. We reviewed the novel findings regarding the biological functions of exosomal miRNAs during glioma pathogenesis and immune regulation. Furthermore, we elaborated on their potential clinical applications as biomarkers in glioma diagnosis, prognosis and treatment response prediction. Finally, we summarized the accessible databases that can be employed for exosome-associated miRNAs identification and functional exploration of cancers, including glioma.

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“…CircRNAs that belong to the family of ncRNAs, have covalently closed‐loop structures without 5′ to 3′ polarity and are produced from pre‐mRNA through the backsplicing or exon skipping, which differ from the canonical splicing (Figure 1) (Jeck & Sharpless, 2014; Movahedpour et al, 2021; Salami et al, 2022; X.‐O. Zhang et al, 2016).…”

Section: An Outlook On Circrnasmentioning

confidence: 99%

“…Neurodegenerative diseases (NDs), including Alzheimer's disease (AD), the tremor associated Parkinson's disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), and Huntington's disease (Movahedpour et al, 2021), can undesirably result in a remarkable neuronal degeneration (Dilokthornsakul et al, 2016; Hebert et al, 2013; Marras et al, 2018; Mehta et al, 2018). Among various NDs, PD is the second most substantial age‐dependent disease, after AD (Cacabelos, 2017).…”

Section: Introductionmentioning

confidence: 99%

Novel insights into the role of circular RNAs in Parkinson disease: An emerging renaissance in the management of neurodegenerative diseases

Dorostgou

Yadegar

Dorostgou

et al. 2022

J of Neuroscience Research

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Parkinson's disease (PD), as a debilitating neurodegenerative disease, particularly affects the elderly population, and is clinically identified by resting tremor, rigidity, and bradykinesia. Pathophysiologically, PD is characterized by an early loss of dopaminergic neurons in the Substantia nigra pars compacta, accompanied by the extensive aggregation of alpha-synuclein (α-Syn) in the form of Lewy bodies. The onset of PD has been reported to be influenced by multiple biological molecules. In this context, circular RNAs (circRNAs), as tissue-specific noncoding RNAs with closed structures, have been recently demonstrated to involve in a set of PD's pathogenic processes.These RNA molecules can either up-or downregulate the expression of α-Syn, as well as moderating its accumulation through different regulatory mechanisms, in which targeting microRNAs (miRNAs) is considered the most common pathway. Since circR-NAs have prominent structural and biological characteristics, they could also be considered as promising candidates for PD diagnosis and treatment. Unfortunately, PD has become a global health concern, and a large number of its pathogenic processes are still unclear; thus, it is crucial to elucidate the ambiguous aspects of PD pathophysiology to improve the efficiency of diagnostic and therapeutic strategies. In line with this fact, the current review aims to highlight the interplay between circRNAs and PD pathogenesis, and then discusses the diagnostic and therapeutic potential of circRNAs in PD progression. This study will thus be the first of its kind reviewing the relationship between circRNAs and PD.

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Exosomal noncoding RNAs: key players in glioblastoma drug resistance

Cited by 39 publications

References 123 publications

Extracellular Vesicles Secreted by Glioma Stem Cells Are Involved in Radiation Resistance and Glioma Progression

Extracellular Vesicles Secreted by Glioma Stem Cells Are Involved in Radiation Resistance and Glioma Progression

Current Understanding of Exosomal MicroRNAs in Glioma Immune Regulation and Therapeutic Responses

Novel insights into the role of circular RNAs in Parkinson disease: An emerging renaissance in the management of neurodegenerative diseases

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