Exosomal circRNA 0001445 promotes glioma progression through miRNA-127-5p/SNX5 pathway

Han, Yonggang; Liu, Yunchao; Zhang, Baoxu; Yin, Gangfeng

doi:10.18632/aging.203013

Cited by 25 publications

(20 citation statements)

References 42 publications

(45 reference statements)

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“…Past studies indicated that circRNAs could be packaged into exosomes and play an important role in the progression of tumours [ 38 , 39 ]. Then, to investigate whether circNEIL3 can be loaded into exosomes, we collected exosomes from the supernatants of cultured GBM cells, which exhibited similar typical cup-shaped morphology, size, and number (Fig.…”

Section: Resultsmentioning

confidence: 99%

EWSR1-induced circNEIL3 promotes glioma progression and exosome-mediated macrophage immunosuppressive polarization via stabilizing IGF2BP3

et al. 2022

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Background Gliomas are the most common malignant primary brain tumours with a highly immunosuppressive tumour microenvironment (TME) and poor prognosis. Circular RNAs (circRNA), a newly found type of endogenous noncoding RNA, characterized by high stability, abundance, conservation, have been shown to play an important role in the pathophysiological processes and TME remodelling of various tumours. Methods CircRNA sequencing analysis was performed to explore circRNA expression profiles in normal and glioma tissues. The biological function of a novel circRNA, namely, circNEIL3, in glioma development was confirmed both in vitro and in vivo. Mechanistically, RNA pull-down, mass spectrum, RNA immunoprecipitation (RIP), luciferase reporter, and co-immunoprecipitation assays were conducted. Results We identified circNEIL3, which could be cyclized by EWS RNA-binding protein 1(EWSR1), to be upregulated in glioma tissues and to correlate positively with glioma malignant progression. Functionally, we confirmed that circNEIL3 promotes tumorigenesis and carcinogenic progression of glioma in vitro and in vivo. Mechanistically, circNEIL3 stabilizes IGF2BP3 (insulin-like growth factor 2 mRNA binding protein 3) protein, a known oncogenic protein, by preventing HECTD4-mediated ubiquitination. Moreover, circNEIL3 overexpression glioma cells drives macrophage infiltration into the tumour microenvironment (TME). Finally, circNEIL3 is packaged into exosomes by hnRNPA2B1 and transmitted to infiltrated tumour associated macrophages (TAMs), enabling them to acquire immunosuppressive properties by stabilizing IGF2BP3 and in turn promoting glioma progression. Conclusions This work reveals that circNEIL3 plays a nonnegligible multifaceted role in promoting gliomagenesis, malignant progression and macrophage tumour-promoting phenotypes polarization, highlighting that circNEIL3 is a potential prognostic biomarker and therapeutic target in glioma.

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Section: Resultsmentioning

confidence: 99%

EWSR1-induced circNEIL3 promotes glioma progression and exosome-mediated macrophage immunosuppressive polarization via stabilizing IGF2BP3

et al. 2022

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“…Additionaly, tumor-released exosomal circ-PDE8A absorbed miR-338 to regulate metastasis associated in colon cancer 1 and promoted the invasive growth of pancreatic ductal adenocarcinoma cells via the metastasis associated in colon cancer /MET/extracellular regulated protein kinases or protein kinase B pathways [ 12 ]. Further, exosomal circRNA 0001445 servered as a sponge for miRNA-127-5p to increase sorting nexin 5 expression and then facilitate the progression of glioma [ 13 ]. Notably, using high-throughput sequencing, Yang et al [ 14 ] found that exosomes extracted from the sera of PTC patients displayed upregulated hsa_circ_007293 (circ007293) expression.…”

Section: Introductionmentioning

confidence: 99%

Exosomal circular RNA hsa_circ_007293 promotes proliferation, migration, invasion, and epithelial–mesenchymal transition of papillary thyroid carcinoma cells through regulation of the microRNA-653-5p/paired box 6 axis

Lin

Hou

et al. 2021

Bioengineered

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Circular RNAs (circRNAs) or exosomes have been reported to exert key regulatory and/or communication functions in human cancer. Nevertheless, current literature on the effects of exosomal circRNAs on tumor invasion and metastasis in thyroid cancer is incomplete. The role of tumor-derived exosomes in driving in vitro papillary thyroid carcinoma (PTC) progression and metastasis requires further investigation. In our study, Exosomes were harvested from PTC patient serum and PTC cell culture medium. Gene expression analysis in PTC cell lines and exosomes was performed with quantitative reverse-transcription polymerase chain reaction. Transwell, wound healing, Western blot assays, and the cell counting kit-8 were applied for functional analysis. Dual-luciferase reporter assay was used to examine the interaction between hsa_circ_007293 (circ007293), microRNA (miR)-653-5p, and paired box 6 (PAX6). Results showed that circ007293 was enriched in exosomes derived from PTC patient serum and cell culture media. Moreover, circ007293 could enter PTC cells through exosomes, and exosomal circ007293 promoted PTC cell epithelial–mesenchymal transition, invasion, migration, and proliferation. circ007293 knockdown reversed the malignant phenotype of PTC cells in vitro . Additionally, circ007293 could competitively bind with miR-653-5p to regulate PAX6 expression. Notably, miR-653-5p overexpression or PAX6 inhibition suppressed the malignant effects of exosomal circ007293. These results evidenced that exosomal circ007293 induced EMT and augmented the invasive and migratory abilities of PTC cells via the miR-653-5p/PAX6 axis, suggesting that it may serve as a promising biomarker for cancer progression.

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“…This mechanism provides a new explanation for arsenite-induced cancer. Glioma-derived exosomal circRNA-0001445 ( Han et al, 2021 ) significantly promotes proliferation and inhibits the apoptosis of glioma cells via the miRNA-1275p/SNX5 signaling pathway. Shi et al ( Xiao and Shi, 2020 ) found that exosomal circRNA_400068 produced by renal cell carcinoma cells promotes the proliferation of healthy kidney cells, significantly inhibits their apoptosis, and promotes their transformation to malignancy, which may be due to signaling through regulation of the miRNA-210-5p/SocS1 axis pathway.…”

Section: Biological Characteristics Of Exosomal Circrnasmentioning

confidence: 99%

Exosomal circRNAs: Emerging Players in Tumor Metastasis

Zhou

et al. 2021

Front. Cell Dev. Biol.

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Metastasis is an important feature of malignant tumors, and is the primary cause of poor prognosis and treatment failure, in addition to representing a potentially fatal challenge for cancer patients. Exosomes are small extracellular vesicles 30–150 nm in diameter that transmit cargo, such as DNA, RNA, and proteins, as a means of intercellular communication. Exosomes play crucial roles in a range of human diseases, especially malignant tumors. A growing number of studies have verified that circRNAs can be enveloped in exosomes and transferred from secretory cells to recipient cells, thereby regulating tumor progression, especially tumor metastasis. Exosomal circRNAs regulate tumor cell metastasis not only by regulating the signaling pathways, but also by affecting the tumor microenvironment. Moreover, exosomal circRNAs have the potential to serve as valuable diagnostic biomarkers and novel therapeutic targets in cancer patients. In this review, we summarize the mechanism by which exosomal circRNAs modulate metastatic phenomena in various types of tumors, and put forward the prospects of clinical applications of exosomal circRNAs in tumor therapy.

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Exosomal circRNA 0001445 promotes glioma progression through miRNA-127-5p/SNX5 pathway

Cited by 25 publications

References 42 publications

EWSR1-induced circNEIL3 promotes glioma progression and exosome-mediated macrophage immunosuppressive polarization via stabilizing IGF2BP3

EWSR1-induced circNEIL3 promotes glioma progression and exosome-mediated macrophage immunosuppressive polarization via stabilizing IGF2BP3

Exosomal circular RNA hsa_circ_007293 promotes proliferation, migration, invasion, and epithelial–mesenchymal transition of papillary thyroid carcinoma cells through regulation of the microRNA-653-5p/paired box 6 axis

Exosomal circRNAs: Emerging Players in Tumor Metastasis

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