Analysis of exosome-derived microRNAs reveals insights of intercellular communication during invasion of breast, prostate and glioblastoma cancer cells

Lessi, Francesca; Aretini, Paolo; Rizzo, Milena; Morelli, Maria Sole; Menicagli, Michele; Franceschi, Sara; Mazzanti, Chiara Maria

doi:10.1080/19336918.2021.1935407

Cited by 4 publications

(5 citation statements)

References 80 publications

(87 reference statements)

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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: 92%

“…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 ). This is probably due to the type and heterogeneity of the cell lines studied; nevertheless, it indicates that EVs do specifically package certain miRNAs to modulate the tumour microenvironment and the intercellular communication between tumour cells and the surroundings.…”

Section: Discussionsupporting

confidence: 92%

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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: 92%

Section: Discussionsupporting

confidence: 92%

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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“…The MicroRNAs (miRNAs) regulate gene expressions in tumor and tumor-adjacent tissue [72]. Lorusso et al explained that miRNAs could facilitate communication between tumor cells and their surroundings and control tumor immunity by directly regulating genes associated with immune stimulation or inactivation [73].…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics Characterization of Candidate Genes Associated with Gene Network and miRNA Regulation in Esophageal Squamous Cell Carcinoma Patients

et al. 2022

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The present study aimed to identify potential therapeutic targets for esophageal squamous cell carcinoma (ESCC). The gene expression profile GSE161533 contained 84 samples, in that 28 tumor tissues and 28 normal tissues encoded as ESCC patients were retrieved from the Gene Expression Omnibus database. The obtained data were validated and screened for differentially expressed genes (DEGs) between normal and tumor tissues with the GEO2R tool. Next, the protein–protein network (PPI) was constructed using the (STRING 2.0) and reconstructed with Cytoscape 3.8.2, and the top ten hub genes (HGsT10) were predicted using the Maximal Clique Centrality (MCC) algorithm of the CytoHubba plugin. The identified hub genes were mapped in GSE161533, and their expression was determined and compared with The Cancer Genome Atlas (TCGA.) ESCC patient’s samples. The overall survival rate for HGsT10 wild and mutated types was analyzed with the Gene Expression Profiling Interactive Analysis2 (GEPIA2) server and UCSC Xena database. The functional and pathway enrichment analysis was performed using the WebGestalt database with the reference gene from lumina human ref 8.v3.0 version. The promoter methylation for the HGsT10 was identified using the UALCAN server. Additionally, the miRNA-HGsT10 regulatory network was constructed to identify the top ten hub miRNAs (miRT10). Finally, we identified the top ten novel driving genes from the DEGs of GSE161533 ESCC patient’s sample using a multi-omics approach. It may provide new insights into the diagnosis and treatment for the ESCC affected patients early in the future.

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“…Exosomes are present in almost all body fluids, including plasma/serum, saliva, breast milk, cerebrospinal fluid, urine and semen (131)(132)(133)(134)(135)(136)(137)(138)(139)(140)(141). Exosomes are also distributed in the TME and carry cargo including a variety of proteins, DNA, mRNA, miRNA, long noncoding RNA, and even virus/prion genetic material (142)(143)(144)(145)(146). Exosomes play a key role in local and remote intercellular communication in cancer and are an important part of the TME.…”

Section: Exosomesmentioning

confidence: 99%

The Role of the Tumor Microenvironment and Treatment Strategies in Colorectal Cancer

Chen

Zheng

2021

Front. Immunol.

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Colorectal cancer (CRC) has the second highest mortality rate among all cancers worldwide. Surgery, chemotherapy, radiotherapy, molecular targeting and other treatment methods have significantly prolonged the survival of patients with CRC. Recently, the emergence of tumor immunotherapy represented by immune checkpoint inhibitors (ICIs) has brought new immunotherapy options for the treatment of advanced CRC. As the efficacy of ICIs is closely related to the tumor immune microenvironment (TME), it is necessary to clarify the relationship between the immune microenvironment of CRC and the efficacy of immunotherapy to ensure that the appropriate drugs are selected. We herein review the latest research progress in the immune microenvironment and strategies related to immunotherapy for CRC. We hope that this review helps in the selection of appropriate treatment strategies for CRC patients.

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Analysis of exosome-derived microRNAs reveals insights of intercellular communication during invasion of breast, prostate and glioblastoma cancer cells

Abstract: Mazzanti (2021) Analysis of exosomederived microRNAs reveals insights of intercellular communication during invasion of breast, prostate and glioblastoma cancer cells,

Cited by 4 publications

References 80 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

Bioinformatics Characterization of Candidate Genes Associated with Gene Network and miRNA Regulation in Esophageal Squamous Cell Carcinoma Patients

The Role of the Tumor Microenvironment and Treatment Strategies in Colorectal Cancer

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