Hypoxic Cancer-Secreted Exosomal miR-182-5p Promotes Glioblastoma Angiogenesis by Targeting Kruppel-Like Factor 2 and 4

Li, Junjun; Yuan, Hongliang; Xu, Hao; Zhao, Hongyang; Xiong, Nanxiang

doi:10.2139/ssrn.3398516

Cited by 16 publications

(41 citation statements)

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“…The exosomes were purified by ultracentrifugation according to standard operating procedures. For more detailed protocols, please refer to our previous articles (13).…”

Section: Isolation and Identification Of Exosomesmentioning

confidence: 99%

Hypoxic Glioma Stem Cell–Derived Exosomes Containing Linc01060 Promote Progression of Glioma by Regulating the MZF1/c-Myc/HIF1α Axis

et al. 2021

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Glioma stem cells (GSC) are a subpopulation of tumor cells with special abilities to proliferate and differentiate in gliomas. They are one of the main causes of tumor recurrence, especially under hypoxic conditions. Although long noncoding RNAs (lncRNA) are known to be involved in numerous biological processes and are implied in the occurrence of certain diseases, their role in tumor development and progression remains poorly understood. Here we explored the mechanisms by which lncRNA derived from hypoxic GSCs (H-GSC) cause glioma progression. Isolation and identification of the Linc01060 gene, the exosomes containing them, and the proteins from tumor cells regulating the gene allowed for studying the effects of Linc01060 on proliferation and glycometabolism. H-GSC exerted their effects by transferring exosomes to glioma cells, resulting in a significant increase in Linc01060 levels. Mechanistically, Linc01060 directly interacted with the transcription factor myeloid zinc finger 1 (MZF1) and enhanced its stability. Linc01060 facilitated nuclear translocation of MZF1 and promoted MZF1-mediated c-Myc transcriptional activities. In addition, c-Myc enhanced the accumulation of the hypoxia-inducible factor-1 alpha (HIF1a) at the posttranscriptional level. HIF1a bound the hormone response elements of the Linc01060 promoter, upregulating the transcription of Linc01060 gene. Clinically, Linc01060 was upregulated in glioma and was significantly correlated with tumor grade and poor clinical prognosis. Overall, these data show that secretion of Linc01060-containing exosomes from H-GSCs activates prooncogenic signaling pathways in glioma cells to promote disease progression.Significance: These findings suggest that inhibition of Linc01060containing exosomes or targeting the Linc01060/MZF1/c-Myc/ HIF1a axis may be an effective therapeutic strategy in glioma.

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“…The exosomes were purified by ultracentrifugation according to standard operating procedures. For more detailed protocols, please refer to our previous articles (13).…”

Section: Isolation and Identification Of Exosomesmentioning

confidence: 99%

Hypoxic Glioma Stem Cell–Derived Exosomes Containing Linc01060 Promote Progression of Glioma by Regulating the MZF1/c-Myc/HIF1α Axis

et al. 2021

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“…Accumulation of miRNA‐182‐5p in exosomes isolated from hypoxic GBM cells stimulates angiogenesis by suppressing Kruppel‐like factor 2 and 4, and consequently up‐regulates VEGFR in ECs. Furthermore, exosomal miRNA‐182‐5p was found to increase vascular permeability through inhibition of tight junction related proteins (such as Occludin, ZO‐1 and Claudin‐5) in ECs …”

Section: Exosomes In Hypoxia Conditionsmentioning

confidence: 99%

How hypoxia regulate exosomes in ischemic diseases and cancer microenvironment?

et al. 2020

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Exosomes, as natural occurring vesicles, play highly important roles in the behavior and fate of ischemic diseases and different tumors. Secretion, composition, and function of exosomes are remarkably influenced by hypoxia in ischemic diseases and tumor microenvironment. Exosomes secreted from hypoxic cells affect development, growth, angiogenesis, and progression in ischemic diseases and tumors through a variety of signaling pathways. In this review article, we discuss how hypoxia affects the quantity and quality of exosomes, and review the mechanisms by which hypoxic cell‐derived exosomes regulate ischemic cell behaviors in both cancerous and noncancerous cells.

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“…26 Among them, exosome is an important medium, which can be involved in the regulation of tumor migration, angiogenesis and drug resistance. 27 In the present study, we found for the first time that lncRNA ROR1-AS1 could be packaged in exosomes, which targetedly inhibited the expression of miR-4686 and promoted the progression of glioma. Exosomes are small vesicles secreted by cells to the outside, which contain signal transduction receptors, bioactive lipids, nucleic acids and proteins.…”

Section: Discussionmentioning

confidence: 50%

<p>Exosomal lncRNA ROR1-AS1 Derived from Tumor Cells Promotes Glioma Progression via Regulating miR-4686</p>

Chai¹,

Wu²,

Liang³

et al. 2020

IJN

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Objective Glioma is one of the most common central nervous system malignant tumors, accounting for 45%–60% of adult intracranial tumors. However, the clinical treatment of glioma is limited. It is of great significance to seek new therapeutic methods for glioma via gene therapy. Materials and Methods Microarray is used to identify the lncRNAs that are differentially expressed in glioma. The expression of long non-coding RNA (lncRNA) ROR1-AS1 and miR-4686 was detected by qRT-PCR. Exosomes were isolated from the supernatant of normal and cancerous cells, and TEM was used for exosomes identification. MTT assay, wound healing assay, transwell assay, and colony formation assay were used to detect the exo-ROR1-AS1 function on proliferation, migration, and invasion in glioma cells. Luciferase assay and RIP assay were used to identify the relationship between lncRNA ROR1-AS1 and miR-4686. The effect of exo-ROR1-AS1 on tumorigenesis of glioma was confirmed by the xenograft nude mice model. Results ROR1-AS1 was up-regulated in glioma tissues, and the high expression of ROR1-AS1 indicated a poor prognosis in glioma patients. Interestingly, ROR1-AS1 was packaged into exosomes and derived from tumor cells. Functional analysis showed exo-ROR1-AS1 promoted the progression of glioma cell lines SHG44 and U251. Furthermore, ROR1-AS1 acted as a sponge of miR-4686 and inhibited its expression. Functionally, forced expression of miR-4686 removed the promoted effects of lncRNA ROR1-AS1 on glioma development. In vivo tumorigenesis experiments showed that exo-ROR1-AS1 promoted glioma development via miR-4686 axis. Conclusion Our study suggested tumor cells derived exo-ROR1-AS1 promoted glioma progression by inhibiting miR-4686, which might be a potential therapeutic target for glioma clinical treatment.

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Hypoxic Cancer-Secreted Exosomal miR-182-5p Promotes Glioblastoma Angiogenesis by Targeting Kruppel-Like Factor 2 and 4

Cited by 16 publications

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Hypoxic Glioma Stem Cell–Derived Exosomes Containing Linc01060 Promote Progression of Glioma by Regulating the MZF1/c-Myc/HIF1α Axis

Hypoxic Glioma Stem Cell–Derived Exosomes Containing Linc01060 Promote Progression of Glioma by Regulating the MZF1/c-Myc/HIF1α Axis

How hypoxia regulate exosomes in ischemic diseases and cancer microenvironment?

<p>Exosomal lncRNA ROR1-AS1 Derived from Tumor Cells Promotes Glioma Progression via Regulating miR-4686</p>

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