Hypoxic glioma‐derived extracellular vesicles harboring MicroRNA‐10b‐5p enhance M2 polarization of macrophages to promote the development of glioma

Li, Bingzhen; Yang, Cheng Chieh; Zhu, Zhanpeng; Chen, Hao; Qi, Bin

doi:10.1111/cns.13905

Cited by 25 publications

(17 citation statements)

References 43 publications

(92 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, miR-10b-5p contributes to glioma progression by targeting HOXB3 and WWC3 (38,39). Furthermore, miR-10b-5p, which is delivered by hypoxic glioma-derived extracellular vesicles, can accelerate macrophage M2 polarization, resulting in the progression of glioma ( 40 ). These results suggested that miR-10b-5p can have both oncogenic and tumor-suppressive roles, depending on the organ and cell type.…”

Section: Discussionmentioning

confidence: 99%

Downregulation of miR‑10b‑5p facilitates the proliferation of uterine leiomyosarcoma cells: A microRNA sequencing‑based approach

et al. 2023

View full text Add to dashboard Cite

Uterine leiomyosarcoma (ULMS) is one of the most aggressive gynecological malignancies. In addition, the molecular background of ULMS has not been fully elucidated due to its low incidence. Therefore, no effective treatment strategies have been established based on its molecular background. The present study aimed to investigate the roles of microRNAs (miRNAs/miRs) in the development of ULMS. Comprehensive miRNA sequencing was performed using six ULMS and three myoma samples, and revealed 53 and 11 significantly upregulated and downregulated miRNAs, respectively. One of the most abundant miRNAs in myoma samples was miR-10b-5p. The mean normalized read count of miR-10b-5p was 93,650 reads in myoma, but only 27,903 reads in ULMS. Subsequently, to investigate the roles of miR-10b-5p, gain-of-function analysis was performed using SK-UT-1 and SK-LMS-1 cell lines. The overexpression of miR-10b-5p suppressed cell proliferation and reduced the number of colonies. Moreover, miR-10b-5p increased the number of cells in the G 1 phase. In conclusion, tumor-suppressive miR-10b-5p was significantly downregulated in ULMS compared with in myoma; thus, miR-10b-5p may serve a specific role in sarcoma progression.

show abstract

Section: Discussionmentioning

confidence: 99%

Downregulation of miR‑10b‑5p facilitates the proliferation of uterine leiomyosarcoma cells: A microRNA sequencing‑based approach

et al. 2023

View full text Add to dashboard Cite

show abstract

“…Indeed, macrophages are phagocytic, and it has been demonstrated that exogenous EVs injected directly into the blood are cleared within two minutes by patrolling monocytes [54]. Previous studies have demonstrated that depending on the origin of the EVs, it can result in their polarization into M1 macrophages ( e.g ., adipocyte-derived EVs from diabetic subjects [55]; hepatocyte-derived EVs from NAFLD patients [56]; EVs from M1 macrophages induced by interferon-γ (IFN-γ) and LPS [57] or M2 (Human umbilical cord mesenchymal stem cell derived-EVs [58]; hypoxic glioma cell-derived EVs [59]). Here, we demonstrated that under HG conditions, M1 macrophages released EVs that can further polarize M0 recipient macrophages into M2 anti-inflammatory macrophages ( i.e .…”

Section: Discussionmentioning

confidence: 99%

M1-derived extracellular vesicles polarize recipient macrophages into M2 and alter skeletal muscle homeostasis in a hyper-glucose environment

Tacconi,

Vari,

Sbarigia

et al. 2023

Preprint

View full text Add to dashboard Cite

BackgroundMacrophages release not only cytokines but also extracellular vesicles (EVs). EVs are small lipid-derived vesicles with virus-like properties transferring lipids, RNA and proteins between cells. Until now, the consequences of macrophage plasticity on the release and the composition of EVs have been poorly explored. In this study, we determined the impact of high-glucose (HG) concentrations on macrophage metabolism, and characterized their derived EV subpopulations. Finally, we determined whether HG-treated macrophage-derived EVs participate in immune responses and in metabolic alterations of skeletal muscle cells.MethodsTHP1-macrophages (M0) were treated with 15mM (MG15) or 30mM (MG30) glucose. M1 or M2 canonical markers, pro– and anti-inflammatory cytokines and lactate production were evaluated. Macrophage-derived EVs were characterized by TEM, flow cytometry, and 1H-Nuclear magnetic resonance spectroscopy for lipid composition. M0 macrophages or C2C12 muscle cells were used as recipients of MG15 and MG30-derived EVs. The lipid profiles of recipient cells were determined, as well as protein and mRNA levels of relevant genes for macrophage polarization or muscle metabolism.ResultsM0 released 2 populations of small and large EVs (sEVs, lEVs) with specific lipid profiles. Proportionally to the glucose concentration, glucose-treatment induced glycolysis in M0 macrophages which consequently shifted into a pro-inflammatory M1 phenotype, containing increased triacylglycerol and cholesterol content. Glucose also affected macrophage sphingolipid and phospholipid compositions. The lipid profile differences between sEVs and lEVs were abolished and represented the lipid profile alterations of MG15 and MG30 macrophages. Both sEVs and lEVs from M15 and M30 macrophages polarized M0 into anti-inflammatory M2, with increased contents of triacylglycerol and cholesterol. MG15 lEVs and sEVs induced insulin-induced AKT hyper-phosphorylation and accumulation of triacylglycerol in muscle cells, a state observed in pre-diabetes. Conversely, MG30 lEVs and sEVs induced insulin resistance in myotubes.ConclusionsAs inflammation involves first M1 macrophages, then the activation of M2 macrophages to attenuate inflammation, this study demonstrates that the dialog between macrophages through the EV route is an intrinsic part of the inflammatory response. In a hyperglycemic context, EV macrophages could participate in the development of muscle insulin-resistance and chronic inflammation.

show abstract

“…In addition, NEDD4L was demonstrated to degrade the catalytic subunit PI3KCA of PI3Ks via the ubiquitin‐proteasome pathway (Wang et al, 2016). Meanwhile, hypoxic gliomas reduce NEDD4L expression in macrophages by secreting MicroRNA‐10b‐5p vesicles to counteract the inhibitory effect of NEDD4L on the PI3K/AKT pathway and M2‐like polarization of TAMs (Li et al, 2022). Interestingly, M2‐like TAMs can also regulate NEDD4L in tumor cells through exosomes, further affecting autophagy and aerobic glycolysis in cancer cells via UPS and promoting tumor progression (Feng et al, 2021; Wang, Wang et al, 2021).…”

Section: Effect Of the Ups On Tamsmentioning

confidence: 99%

Role of the ubiquitin–proteasome system on macrophages in the tumor microenvironment

Xiao,

Liu,

et al. 2024

Journal Cellular Physiology

View full text Add to dashboard Cite

Tumor‐associated macrophages (TAMs) are key components of the tumor microenvironment, and their different polarization states play multiple roles in tumors by secreting cytokines, chemokines, and so on, which are closely related to tumor development. In addition, the enrichment of TAMs is often associated with poor prognosis of tumors. Thus, targeting TAMs is a potential tumor treatment strategy, in which therapeutic approaches such as reducing TAMs numbers, remodeling TAMs phenotypes, and altering their functions are being extensively investigated. Meanwhile, the ubiquitin–proteasome system (UPS), an important mechanism of protein hydrolysis in eukaryotic cells, participates in cellular processes by regulating the activity and stability of key proteins. Interestingly, UPS plays a dual role in the process of tumor development, and its role in TAMs deserve to be investigated in depth. This review builds on this foundation to further explore the multiple roles of UPS on TAMs and identifies a promising approach to treat tumors by targeting TAMs with UPS.

show abstract

Hypoxic glioma‐derived extracellular vesicles harboring MicroRNA‐10b‐5p enhance M2 polarization of macrophages to promote the development of glioma

Cited by 25 publications

References 43 publications

Downregulation of miR‑10b‑5p facilitates the proliferation of uterine leiomyosarcoma cells: A microRNA sequencing‑based approach

Downregulation of miR‑10b‑5p facilitates the proliferation of uterine leiomyosarcoma cells: A microRNA sequencing‑based approach

M1-derived extracellular vesicles polarize recipient macrophages into M2 and alter skeletal muscle homeostasis in a hyper-glucose environment

Role of the ubiquitin–proteasome system on macrophages in the tumor microenvironment

Contact Info

Product

Resources

About