Analysis of miR-9-5p, miR-124-3p, miR-21-5p, miR-138-5p, and miR-1-3p in Glioblastoma Cell Lines and Extracellular Vesicles

Zottel, Alja; Šamec, Neja; Kump, Ana; Dall'Olio, Lucija Raspor; Dominkuš, Pia Pužar; Romih, Rok; Hudoklin, Samo; Mlakar, Jernej; Nikitin, Daniil; Sorokin, Maxim; Buzdin, Anton; Jovčevska, Ivana; Komel, Radovan

doi:10.3390/ijms21228491

Cited by 36 publications

(27 citation statements)

References 75 publications

(123 reference statements)

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“…MiR-21 is a well-studied miRNA, which acts as an oncomir and associates with a malignant phenotype [ 4 , 49 ]. It has been very recently reported being significantly downregulated in GBM CSCs compared to astrocytes [ 11 ] and has already been shown to associate with a more differentiated phenotype [ 50 , 51 ]. The primary CSCs utilized in the present manuscript have been assessed molecularly and resulted to belong mostly to the proneural transcriptional subgroup [ 52 , 53 ].…”

Section: Discussionmentioning

confidence: 99%

“…GBM prognosis is generally poor and the median survival is only 14 months, while the 5-year survival rate is unfortunately between 5%–10% [ 7 , 8 , 9 , 10 ]. Overall, 90% of GBM originate de novo while the remaining 10% arise from lower-grade glioma [ 11 , 12 ]. Although the exact etiology of GBM is still being explored, it has been reported that ionizing radiation at high-dose and rare genetic disorders could facilitate the onset of GBM [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

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MicroRNA Expression Profile Distinguishes Glioblastoma Stem Cells from Differentiated Tumor Cells

Tomei

Volonté

Ravindran

et al. 2021

JPM

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Glioblastoma (GBM) represents the most common and aggressive tumor of the brain. Despite the fact that several studies have recently addressed the molecular mechanisms underlying the disease, its etiology and pathogenesis are still poorly understood. GBM displays poor prognosis and its resistance to common therapeutic approaches makes it a highly recurrent tumor. Several studies have identified a subpopulation of tumor cells, known as GBM cancer stem cells (CSCs) characterized by the ability of self-renewal, tumor initiation and propagation. GBM CSCs have been shown to survive GBM chemotherapy and radiotherapy. Thus, targeting CSCs represents a promising approach to treat GBM. Recent evidence has shown that GBM is characterized by a dysregulated expression of microRNA (miRNAs). In this study we have investigated the difference between human GBM CSCs and their paired autologous differentiated tumor cells. Array-based profiling and quantitative Real-Time PCR (qRT-PCR) were performed to identify miRNAs differentially expressed in CSCs. The Cancer Genome Atlas (TCGA) data were also interrogated, and functional interpretation analysis was performed. We have identified 14 miRNAs significantly differentially expressed in GBM CSCs (p < 0.005). MiR-21 and miR-95 were among the most significantly deregulated miRNAs, and their expression was also associated to patient survival. We believe that the data provided here carry important implications for future studies aiming at elucidating the molecular mechanisms underlying GBM.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

MicroRNA Expression Profile Distinguishes Glioblastoma Stem Cells from Differentiated Tumor Cells

Tomei

Volonté

Ravindran

et al. 2021

JPM

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“…MiR-21 represents a key regulator of the EMT signaling that has been shown to be one of the earlier players in CSC/CIC formation [ 203 ]. MiR-21 has also been reported in another study to be down-regulated in GBM CSCs/CICs as compared to astrocytes [ 204 ] and shown to be associated with a differentiated phenotype in GBM [ 205 , 247 ].…”

Section: The Dual Role Of Micrornas In Orchestrating Pro-tumoral Amentioning

confidence: 95%

Cancer Stem Cells Are Possible Key Players in Regulating Anti-Tumor Immune Responses: The Role of Immunomodulating Molecules and MicroRNAs

Tomei

Ibnaof

Ravindran

et al. 2021

Cancers

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Cancer cells endowed with stemness properties and representing a rare population of cells within malignant lesions have been isolated from tumors with different histological origins. These cells, denominated as cancer stem cells (CSCs) or cancer initiating cells (CICs), are responsible for tumor initiation, progression and resistance to therapies, including immunotherapy. The dynamic crosstalk of CSCs/CICs with the tumor microenvironment orchestrates their fate and plasticity as well as their immunogenicity. CSCs/CICs, as observed in multiple studies, display either the aberrant expression of immunomodulatory molecules or suboptimal levels of molecules involved in antigen processing and presentation, leading to immune evasion. MicroRNAs (miRNAs) that can regulate either stemness properties or their immunological profile, with in some cases dual functions, can provide insights into these mechanisms and possible interventions to develop novel therapeutic strategies targeting CSCs/CICs and reverting their immunogenicity. In this review, we provide an overview of the immunoregulatory features of CSCs/CICs including miRNA profiles involved in the regulation of the interplay between stemness and immunological properties.

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“…miRNAs are short sequence single-stranded RNAs with a major role in gene regulation (19). Several in vitro studies using microarray have shown the involvement of miRNAs (including miR-21, mir-29 miR-210, miR-148, and many others) in enhancing proliferation and inhibiting tumor cell apoptosis in GBM (20)(21)(22)(23)(24)(25). mir-21 has been mostly studied as a major GBM cell regulator (26) and has also been shown to be transferred in the cargo of GBM EVs (27).…”

Section: Role Of Evs In Glioma What Can They Do?mentioning

confidence: 99%

Glioma-Derived Extracellular Vesicles – Far More Than Local Mediators

Tankov

Walker

2021

Front. Immunol.

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Extracellular vesicle (EV) secretion is a ubiquitous cellular process with both physiologic and pathologic consequences. EVs are small lipid bilayer vesicles that encompass both microvesicles and exosomes and which are secreted by virtually all cells including cancer cells. In this review, we will focus on the roles of EVs in mediating the crosstalk between glioblastoma (GBM) cells and innate and adaptive immune cells and the potential impact on glioma progression. Glioma-derived EVs contain many bioactive cargoes that can broaden and amplify glioma cell mediated immunosuppressive functions and thereby contribute to shaping the tumor microenvironment. We will discuss evidence demonstrating that the low oxygen (hypoxia) in the GBM microenvironment, in addition to cell-intrinsic effects, can affect intercellular communication through EV release, raising the possibility that properties of the tumor core can more widely impact the tumor microenvironment. Recent advances in glioma-derived EV research have shown their importance not only as message carriers, but also as mediators of immune escape, with the capacity to reprogram tumor infiltrating immune cells. Exploring EV function in cancer-immune crosstalk is therefore becoming an important research area, opening up opportunities to develop EV monitoring for mechanistic studies as well as novel diagnostic glioma biomarker applications. However, robust and reproducible EV analysis is not always routinely established, whether in research or in clinical settings. Taking into account the current state of the art in EV studies, we will discuss the challenges and opportunities for extending the many exciting findings in basic research to a better interpretation of glioma and its response to current and future immunotherapies.

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Analysis of miR-9-5p, miR-124-3p, miR-21-5p, miR-138-5p, and miR-1-3p in Glioblastoma Cell Lines and Extracellular Vesicles

Cited by 36 publications

References 75 publications

MicroRNA Expression Profile Distinguishes Glioblastoma Stem Cells from Differentiated Tumor Cells

MicroRNA Expression Profile Distinguishes Glioblastoma Stem Cells from Differentiated Tumor Cells

Cancer Stem Cells Are Possible Key Players in Regulating Anti-Tumor Immune Responses: The Role of Immunomodulating Molecules and MicroRNAs

Glioma-Derived Extracellular Vesicles – Far More Than Local Mediators

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